Incidence Of Abnormal Karyotype Research Articles

Cytogenetic Profile in Monoclonal Gammopathy of Undetermined Significance, Smoldering and Symptomatic Multiple Myeloma: A Study of 1087 Patients with Highly Purified Plasma Cells

The aim of this study was to examine the cytogenetic profiles of plasma cell neoplasms (PCNs) at various disease stages, encompassing 1087 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed multiple myeloma (NDMM), and refractory/relapsed multiple myeloma (RRMM). Fluorescence in situ hybridization (FISH) analyses were conducted on highly purified plasma cell samples, revealing that 96% of patients exhibited at least one cytogenetic abnormality. The genomic complexity escalated from MGUS to SMM and further to NDMM and RRMM, largely driven by 1q gain, del(17p), MYC-rearrangement (MYC-R), del(1p), and tetraploidy. Elevated frequencies of high-risk cytogenetics (59%), 1q gain (44%), and del(17p) (23%), as well as the presence of subclones (48%), were particularly notable in RRMM cases. IGH::CCND1 was observed in 26% of the cases, with no apparent variations across races, ages, or disease groups. Concurrent chromosomal analysis with FISH revealed that the incidence of abnormal karyotypes was strongly correlated with the extent of neoplastic plasma cell infiltration, genomic complexity, and the presence of specific abnormalities like del(17p) and MYC-R. Approximately 98% of the cases with abnormal karyotypes were complex, with most featuring five or more abnormalities. Chromosome 1 structural abnormalities were the most prevalent, found in 65% of cases. The frequent presence of subclones and composite karyotypes underscored the genomic heterogeneity and instability in this cohort.

The de novo aberration rate of prenatal karyotype was comparable between 1496 fetuses conceived via IVF/ICSI and 1396 fetuses from natural conception.

To evaluate the cytogenetic risk of assisted reproductive technology (ART) by comparing the incidence of de novo chromosomal abnormalities between fetuses conceived via in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and natural conception. Prenatal invasive diagnostic testing (amniocentesis and cytogenetic analysis) was performed on 1496 fetuses conceived via IVF/ICSI (IVF/ICSI group) and 1396 fetuses from natural conception (NC group). The incidence of de novo chromosomal abnormalities (including aneuploidy and chromosomal structure abnormalities) was used to evaluate the cytogenetic risk of ART. For statistical analysis, χ2-test was used for binary dependent variable. The significance level was P < 0.05 and confidence interval was 95%. The IVF/ICSI group displayed a modest increase in the overall de novo chromosomal abnormality rate compared with that in the NC group but with no statistical significance (6.75% vs. 6.16%; χ2 = 0.42, P > 0.05). The incidence of abnormal karyotypes was also not significantly different between the IVF/ICSI and NC groups in different maternal ages, including ≥ 35years group (7.55% vs. 9.60%, χ2 = 1.40, P > 0.05) and < 35years group (6.20% vs. 4.54%, χ2 = 2.51, P > 0.05). Moreover, there was no difference in the proportion of aneuploid and structural abnormalities in detected karyotypes between the IVF/ICSI and NC groups. Logistic regression analysis showed no significant association between the method of pregnancy and de novo chromosomal abnormalities (odds ratio (OR) 1.03; 95% CI 0.71-1.50; P = 0.86) after adjusting for other confounding factors. Fetuses conceived via IVF/ICSI had a slight but not statistically significant increase in de novo abnormal karyotypes compared to those in naturally conceived fetuses. Our findings indicate no significant association between de novo fetal chromosomal abnormalities and the pregnancy method in high-risk pregnancies in the second trimester. For these pregnancies with a high risk but with a normal karyotype, further genetic testing is required for diagnosis.

Validation of the Who-Defined 20% Circulating Blasts Threshold for Diagnosis of Acute Leukemia in Myelofibrosis: A Single Center Study of 144 Patients with Blast or Chronic Phase Disease with Excess Blasts

Background:The World Health Organization (WHO)-defined criteria for acute myeloid leukemia (AML), including blast phase myeloproliferative neoplasms (MPN-BP), includes the presence of ≥20% blasts in the peripheral blood (PB), regardless of blast content in the bone marrow (BM) (Blood 2016;127:2391) . It is currently unclear if this 20% threshold is valid for primary myelofibrosis (PMF), in terms of distinguishing PB-defined MPN-BP from either chronic phase disease with excess blasts (PMF-EB; defined by the presence of 5-19% circulating blasts) or BM-defined MPN-BP.Methods:Diagnoses of MPN, including PMF and MPN-BP, were according to WHO criteria (Blood 2016;127:2391). The study population included chronic phase PMF patients with 5-19% circulating blasts (PMF-EB) and MPN patients with blast phase disease (MPN-BP), defined by the presence of ≥20% blasts in PB only (PB-defined MPN-BP) or BM (BM-defined MPN-BP). Statistical analyses for PMF-EB considered clinical and laboratory data collected at the time of documented PB blast count of ≥5% and for MPN-BP, date of leukemic transformation. Phenotypic and prognostic comparisons considered four distinct categories: i) chronic phase disease with 5-9% circulating blasts (PMF-EB-1), ii) chronic phase disease with 10-19% circulating blasts (PMF-EB-2), iii) MPN-BP defined by ≥20% BM blasts (BM-defined) and iv) MPN-BP defined by ≥20% blasts in PB only (PB-defined).Results:The total number of study patients was144 and included 41 patients with PMF-EB and 103 with MPN-BP; the 41 patients with PMF-EB included 28 with PMF-EB-1 (median age 69 years; 61% males) and 13 with PMF-EB-2 (median age 64 years; 54% males); the 103 patients with MPN-BP included 71 BM-defined (median age 68 years; 69% males) and 32 PB-defined (median age 66 years; 72% males) MPN-BP (p=0.6 for age and 0.6 for gender distribution). The four operational groups were also similar in their need for red cell transfusions (p=0.4), hemoglobin level (p=0.9), leukocyte count (p=0.9) and driver mutational status (p=0.3), including incidence of type 1/like CALR mutations (11% for PMF-EB-1 vs 15% for PMF-EB-2 vs 17% for PB-defined MPN-BP vs 19% for BM-defined MPN-BP). Significant differences were noted for platelet count (lower for both PB and BM defined MPN-BP; p=0.004) and incidence of abnormal karyotype (p=0.02) and unfavorable karyotype (22% for PMF-EB-1, 62% PMF-EB-2, 61% PB-defined MPN-BP and 49% BM-defined MPN-BP; p=0.03). Survival data showed significant difference in favor of PMF-EB, compared to both BM- and PB-defined MPN-BP, while they were similar for PMF-EB-1 vs PMF-EB-2 and for PB- vs BM-defined MPN-BP (Figure 1).Conclusions:The observations from the current study support the prognostic validity of current WHO criteria in distinguishing chronic phase PMF with excess blasts (PMF-EB) from PB-defined MPN-BP. The current study also confirms the validity of using circulating blast percentage to define MPN-BP, regardless of BM blast percentage. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cytogenetic characteristics of 665 patients with myelodysplastic syndrome in China: A single‑center report

The karyotype is highly important for diagnosis and prognosis in myelodysplastic syndrome (MDS). The objective of the present study was to investigate the cytogenetic characteristics of patients with MDS in China. The karyotypes of 665 Chinese patients with MDS were analyzed, and it was identified that 298 cases (298/665, 44.8%) had abnormal karyotypes. Among the 298 patients with abnormal karyotypes, the 75 patients with trisomy 8 (+8) constituted the most common subset (75/298, 25.2%). The incidence of abnormal karyotypes was significantly higher in patients who were ≥51 years old compared with those <51 years old, (54.8 vs. 34.7%, respectively; P<0.05). Based on World Health Organization (WHO) classification-based Prognostic Scoring System (WPSS) criteria, the incidence of poor-prognosis karyotypes was significantly higher (17.4 vs. 5.4%; P<0.05) in the older patient group, and based on the Revised International Prognostic Scoring System (IPSS-R) criteria, the incidence of poor-/very poor-prognosis karyotypes was also significantly higher (17.4 vs. 6.6%; P<0.05) in patients ≥51 years old compared with younger ones. Based on the WHO classification of MDS subtypes, the incidence of abnormal karyotypes in patients with high percentages of bone marrow (BM) blasts [excess blasts (EB)-I + EB-II, ≥5% blasts] was significantly higher than that in patients with low percentages of BM blasts (those with single lineage dysplasia + multilineage dysplasia, <5% blasts) (62.5 vs. 36.0%; P<0.05). The incidence of poor-prognosis karyotypes based on WPSS criteria was significantly higher in patients with high percentages of BM blasts than those with low percentages (22.0 vs. 6.9%, respectively; P<0.05), and the incidence of poor-/very poor-prognosis karyotypes based on IPSS-R criteria was also significantly higher (23.0 vs. 7.4%, respectively; P<0.05). These results demonstrate that +8 is the most common abnormal karyotype in Chinese patients with MDS. Age and the percentage of BM blasts are associated with the incidence of both abnormal karyotypes and karyotypes with poor prognosis. The results of cytogenetic abnormalities in this study will supplement the data on patients of MDS in China.

Obstetrical and perinatal outcomes in fetuses with early versus late sonographic diagnosis of short femur length: A single-center, prospective, cohort study

ObjectivesThe aim of this study was to evaluate obstetrical and perinatal outcomes in fetuses with short femur length diagnosed before or after 24 weeks of gestation. Study DesignThis was a prospective cohort study on singleton pregnancies with a diagnosis of fetal femur < 5 centile. Included patients were divided into two groups: patients with a first diagnosis of femur length < 5th percentile at 14-24 weeks (group A) and those with the first diagnosis made at > 24 weeks (group B). Results147 patients were included for the analysis. Group A and group B included 66 (44.9%) and 81 (55.1%) cases. Abnormal fetal karyotype and skeletal dysplasia rates were significantly higher (27.3% vs 3.7%,P < 0.001 and 19.7% vs 3.7%, P = 0.002) in group A. Women in group B had a higher incidence of small for gestational age and intrauterine growth restriction (7.6% vs 24.7%, P = 0.007 and 19.7% vs 44.4%, P = 0.002). There was a significant higher incidence of live births in group B (34.9% vs 97.5%, P < 0.001), while the rate of termination of pregnancy was increased in group A (56.1% vs 1.2%, P < 0.001). No significant difference was found in perinatal outcomes of live births, when comparing group A and B. ConclusionsThe incidence of abnormal karyotype and skeletal dysplasia is higher when short femur length diagnosed earlier in gestation, while the incidence of small for gestational age, intrauterine growth restriction and the rate of live births are significantly increased when short femur length is diagnosed later during pregnancy.

Chromosomal abnormalities after ICSI in relation to semen parameters: results in 1114 fetuses and 1391 neonates from a single center.

Is there a relationship between karyotype abnormalities in fetuses and children conceived by ICSI and their father's semen parameters? The de novo chromosomal abnormality rate in pre- and postnatal karyotypes of ICSI offspring was higher than in the general population and related to fathers' sperm parameters. Several studies have reported a higher rate of de novo chromosomal anomalies in ICSI fetuses but recent data from large cohorts are limited. Overall, reported prevalences of non-inherited karyotype aberrations are increased in fetuses conceived after ICSI and vary between 1.6% and 4.2%. Only a few studies focus on the relation between karyotype anomalies in ICSI offspring and semen parameters of their fathers. Furthermore, an increased incidence of abnormal karyotypes in ICSI neonates has been described, but the rates vary widely across studies. We report on karyotype results from prenatal testing by means of chorionic villus sampling and amniocentesis and results from postnatal blood sampling in offspring conceived by ICSI in a single center. Ongoing pregnancies resulting from an oocyte retrieval between January 2004 and December 2012 and after transfer of fresh ICSI embryos obtained using ejaculated or non-ejaculated sperm (fresh or frozen-thawed) were considered. Pregnancies following frozen embryo transfer, oocyte or sperm donation, IVF, preimplantation genetic testing and IVM were excluded. All abnormal prenatal results after sampling are reported irrespective of the outcome of the pregnancy. From the 4816 ongoing ICSI pregnancies, information on pregnancy outcome was available for 4267 pregnancies. Prenatal testing was performed in 22.3% of the pregnancies, resulting in a diagnosis in 1114 fetuses. A postnatal karyotype was obtained in 29.4% of the pregnancies in which no invasive prenatal diagnosis was performed, resulting in a total of 1391 neonates sampled. The prevalence of chromosomal anomalies according to maternal age and semen quality was analyzed with logistic regression. For definitions of normal semen quality, the World Health Organization reference values for human semen characteristics were adopted. An abnormal fetal karyotype was found in 29 singletons and 12 multiples (41/1114; 3.7%; 95% CI 2.7-4.9%): 36 anomalies were de novo (3.2%; 95% CI 2.3-4.4), either numerical (n = 25), sex (n = 6) or structural (n = 5), and five were inherited. Logistic regression analysis did not show a significant association between maternal age and a de novo chromosomal fetal abnormality (odds ratio (OR) 1.05; 95% CI 0.96-1.15; P = 0.24). In all but one case, fetuses with an abnormal karyotype were conceived by ICSI using ejaculated sperm.Abnormal karyotypes were found in 14 (1.0%; 95% CI 0.6-1.7) out of 1391 postnatal samples of children born after ICSI who were not tested prenatally: 12 were de novo anomalies and two were inherited balanced karyotypes. The 14 abnormal karyotypes were all found in children born after ICSI using ejaculated sperm.The odds of a de novo karyotype aberration increased with maternal age when combining pre- and postnatal data (OR 1.11; 95% CI 1.04-1.19). A higher rate of de novo chromosomal abnormalities was found in fetuses and children of couples with men having a sperm concentration <15 million/ml (adjusted OR (AOR) 2.10; 95% CI 1.14-3.78), sperm concentration <5 million/ml (AOR 1.9; 95% CI 1.05-3.45) and total sperm count <10 million (AOR 1.97; 95% CI 1.04-3.74). We cannot exclude that the observation of a higher prevalence of karyotype anomalies in ICSI offspring compared to literature data in the general population is due to enhanced surveillance after ART given the lack of a control group. Although we did not find more chromosomal anomalies after ICSI with non-ejaculated sperm, the small numbers do not allow firm conclusions. The observed increased risk of a de novo karyotype anomaly after ICSI conception in couples with poor sperm warrants continued counseling toward prenatal testing.The current and widespread use of innovative non-invasive prenatal testing will result in larger datasets, adding to a balanced estimation of the prevalence of karyotype anomalies in ICSI offspring. This study was supported by the Methusalem grants issued by the Vrije Universiteit Brussel. All authors declared no conflict of interest related to this study. N/A.

Clinical characteristics and prognosis of childhood acute lymphoblastic leukemia complicated with EB virus infection

Objective To explore the clinical features and prognosis of childhood acute lymphoblastic leukemia(ALL) complicated with EB virus (EBV) infection. Methods The results of detection of EBV antibody and EBV-DNA in peripheral blood mononuclear cells of 196 children with ALL diagnosed in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2015 to January 2019 were collected. According to the results, 196 children with ALL were divided into EBV infection group and non-EBV infection group. The hepatomegaly and splenomegaly, chromosome, peripheral blood routine, immunophenotyping, clinical risk, secondary infection during chemotherapy, minimal residual disease (MRD) of day 46 after chemotherapy, karyotype, and prognosis were compared between the two groups. The children were followed up until April 30, 2019. Results Among 196 children with ALL, EBV infection rate was 72.96% (143/196). The EBV-DNA level [median (P25, P75)] of peripheral blood mononuclear cells was 3.7×103 copies/L(1.6×103 copies/L, 8.8×103 copies/L). The incidence of hepatosplenomegaly (subcostal ≥ 5 cm) in EBV infection group was higher than that in non-EBV infected group [14.69% (21/143) vs. 3.77% (2/53), χ 2= 4.45, P= 0.035]. There was no significant difference in the number of white blood cells and the incidence of abnormal karyotype between EBV infection group and non-EBV infection group (both P > 0.05). The secondary infection rate in EBV infection group was higher than that in the non-EBV infection group [41.96% (60/143) vs.24.53% (13/53), χ2= 5.03, P= 0.025], and the remission rate of day 46 in EBV-infection group was lower than that in non-EBV infection group [80.42% (115/143) vs. 98.11% (52/53), χ2= 9.60, P= 0.020]. The recurrence rate in EBV-infection group was higher than that in non-EBV infectious group [11.89% (17/143) vs. 1.89% (1/53), χ2= 4.64, P= 0.031], and there was a significant difference in the component ratio of immunophenotyping and clinical risk between the two groups (both P < 0.05). Conclusions The hepatosplenomegaly in children with ALL complicated with EBV infection is obvious, the secondary infection rate is high, the remission rate is low, the recurrence rate is high, and the prognosis is poor. EBV infection may be related to immunophenotyping and clinical risk in children with ALL, and has nothing to do with the abnormal karyotypes. Key words: Leukemia, lymphoid; Herpesvirus 4, human; Epstein-Barr virus; Child; Clinical features; Prognosis

Cytogenetic assessment of Iranian infertile men with undescended testis: A retrospective study.

Objective:Undescended testis (UDT) is a urogenital disease that affects fertility. This study looked into the cytogenetic abnormalities of Iranian infertile patients with UDT.Methods:Our study included 522 infertile patients with UDT (case group) and two control groups, one with 300 infertile men without UDT and another with 268 fertile men.Results:Chromosomal abnormalities were found in 45 patients with UDT (8.62%). Seven of the alterations were considered as normal features. Klinefelter syndrome and mosaicism were the most common anomalies. Chromosomal abnormalities were found in 31 infertile men in the control group (10.33%), 13 of which deemed normal and 18 (6%) anomalous. Nine chromosomal abnormalities were found in the second control group with fertile men (3.35%), six deemed normal and three (1.11%) anomalous.Conclusion: Despite the high rate of abnormalities in infertile controls (6%) and the higher rate seen in infertile individuals with UDT indicate a significant prevalence of chromosomal abnormalities in the Iranian population, particularly when the literature suggests that the normal rate of abnormal karyotypes should be within the 0.7-1% range in the general population. The incidence of abnormal karyotypes increased when infertile patients had additional conditions such as UDT.

Pregnancy and neonatal outcomes of small follicle–derived blastocyst transfer in modified natural cycle in vitro fertilization

To compare the efficacy and safety of blastocyst transfer derived from small follicles (SF; ≤10mm) and large follicles (LF; ≥11mm). Retrospective cohort study. Private clinic. Patients (n = 1,072) 30-40years old who underwent blastocyst transfer (BT; n = 1,247) between January 2012 and December2014. Oocytes retrieved during a modified natural cycle from both LF and SF were fertilized by a conventional method or intracytoplasmic sperm injection. The blastocysts were frozen, thawed, and transferred one by one in the following spontaneous ovulatory cycles or hormone replacement cycles. BT resulted in live births and major congenital anomalies. SF-derived BTs (n = 597) yielded 55 chemical abortions (9.2%), 73 clinical abortions (12.2%), and 261 live births (43.8%), whereas LF-derived BTs (n = 650) yielded 71 chemical abortions (10.9%), 73 clinical abortions (11.2%), and 311 live births (47.9%). These incidences were not statistically different between SF- and LF-derived BTs. The incidence of abnormal karyotypes was also not statistically different between SF- and LF-derived spontaneous abortions (71% [39/55] vs. 72% [40/55], respectively). The incidence of major congenital anomalies in neonates did not differ between SF- and LF-derived pregnancies (1.5% and 1.3%, respectively; relative risk = 1.10, 95% confidence interval [0.55-3.21]). SF-derived BT is as efficacious and safe as LF-derived BT.

Новые горизонты цитогенетики при первичном миелофиброзе

ABSTRACT Aim. To evaluate the potential of a new cytogenetic technique in patients with primary myelofibrosis (PMF). Materials and methods. 48-hour blood cell cultures (accord-ing to Singh et al., 2013) were used for cytogenetic study in 11 PMF patients (5 female, 6 men, aged 32–60 years; median 48.6 years). GTG-banding and different types of fluorescence in situ hybridization (FISH) techniques were used for identifica-tion of chromosomal aberrations. Results. The incidence of abnormal karyotypes in blood cul-tures was significantly higher than that in standard bone mar-row cultures (82 vs 27 %; p < 0.01). The polyploid clones were found in blood cultures of 45 % of patients. Structural chro-mosomal aberrations were found in chromosomes 6, 1, 3, as well as 16 and 17 (in 2 and 1 patients with each aberration, respectively). In all but one patients these abnormalities in dip-loid and polyploid metaphases were identical. Partial 1q tri-somy resulted from adding of additional (1q21–1q44) material translocated to the short arm of chromosome 5 to the material of 2 normal homologue of chromosome 1. It seems that 1q+, i(17q) and some others chromosomal abnormalities were sec-ondary, whereas 6p21 locus involvement may be a primary defect in PMF. The t(3;6)(q25;p21) translocation described for the first time and confirmed by FISH should be considered a variant of well-known translocation t(1;6). Allo-HSCT in 2 pa-tients with 1q+ was successful, whereas there were problems with engraftment in a female patient with prognostically unfa-vorable t(3;3)(q21;q26) translocation associated with the

EP09.29: Outcome of pregnancies complicated with exomphalos in Wales during a 14 year period (1998–2012)

The aim of this study was to review all the cases of fetal exomphalos reported to CARIS (Congenital Anomaly Register and Information Service for Wales) during the period of 1998 to 2012. All congenital anomalies diagnosed during pregnancy or after birth are notified to CARIS in Wales. This database was used to identify all cases of exomphalos diagnosed and reported to CARIS during the period of 1998–2012. The database was searched to find the total number of cases reported, the gestation at which diagnosed, karyotype of fetus, associated structural anomalies and outcome of neonates. A total of 236 cases of exomphalos were reported to CARIS during this 14 year period. Of these, 183 (77.5%) were diagnosed antenatally. A total of 111 (47%) mothers opted for termination. The live births were 93 (39.4%). Karyotype was available for 104 cases of which 73 (70%) were abnormal. Majority of abnormalities were Trisomy 18. In 78.8% of cases, exomphalos was associated with other structural abnormalities. The commonest defects were cardiac (22.5%), spinal (9.7%) and renal (9.7%). This is one of the largest study of exomphalos in pregnancy. There was a high incidence of abnormal karyotype as well as associated structural abnormalities. Of the abnormal karyotypes, Trisomy 18 seemed to be the most common. Cardiac abnormality was the commonest associated structural defect.

Chromosome abnormalities diagnosed in utero: a Japanese study of 28 983 amniotic fluid specimens collected before 22 weeks gestations.

To investigate the frequency and type of abnormal karyotype in Japan by amniocentesis before 22 weeks of gestation. We performed a retrospective analysis of 28 983 amniotic fluid specimens in a local population collected before 22 weeks gestations for fetal karyotyping. The incidence of abnormal karyotype was 6.0%. The main indication was advanced maternal age (AMA) of 35 years and older, which represented over half of the clinical indications. Abnormal karyotype was most frequently reported among the referrals for abnormal ultrasound findings (21.8%), followed by positive maternal serum screen results (5.3%). Three-fourths of abnormal karyotype was either autosomal aneuploidy (64.0%) or sex chromosome aneuploidy (11.6%). Abnormal karyotype was detected in 2.8% of pregnant women referred for AMA. Clinically significant abnormal karyotype increased with advancing maternal age. The frequency and type of abnormal karyotype detected by amniocentesis for various indications were determined. Amniocentesis was mainly performed among the referrals for AMA, which is a characteristic distribution of indications of Japan.

Critical Congenital Heart Disease-Utility of Routine Screening for Chromosomal and Other Extracardiac Malformations

Objective. Infants with critical congenital heart disease (CHD) can have genetic and other extracardiac malformations, which add to the short- and long-term risk of morbidity and perhaps mortality. We sought to examine our center's practice of screening for extracardiac anomalies and to determine the yield of these tests among specific cardiac diagnostic categories. Design. Retrospective review of infants admitted to the cardiac intensive care unit with a new diagnosis of CHD. Subjects were categorized into six groups: septal defects (SD), conotruncal defects (CTD), single-ventricle physiology (SV), left-sided obstructive lesions (LSO), right-sided obstructive lesions (RSO), and "other" (anomalous pulmonary venous return, Ebstein's anomaly). Screening modalities included genetic testing (karyotype and fluorescent in situ hybridization for 22q11.2 deletion), renal ultrasound (RUS), and head ultrasound (HUS). Results. One hundred forty-one patients were identified. The incidence of cardiac anomalies was: CTD (36%), SD (18%), SV (18%), LSO (14%), RSO (3%), and "other" (8%). Overall 14% had an abnormal karyotype, 5% had a deletion for 22q11.2, 28% had an abnormal RUS and 22% had abnormal HUS. Patients in SD and SV had the highest incidence of abnormal karyotype (36% and 17%); 22q11.2 deletion was present only in CTD and LSO groups (9% and 7%, respectively); abnormal RUS and HUS were seen relatively uniformly in all categories. Premature infants had significantly higher incidence of renal 43% vs. 24%, and intracranial abnormalities 46% vs. 16%. Conclusion. Infants with critical CHD and particularly premature infants have high incidence of genetic and other extracardiac anomalies. Universal screening for these abnormalities with ultrasonographic and genetic testing maybe warranted because early detection could impact short and long-term outcomes.

Cytogenetic characteristics and prognosis analysis in 231 myelodysplastic syndrome patients from a single institution

We analyzed the clinical and hematologic data of 231 patients diagnosed with de novo myelodysplastic syndrome (MDS), identified cytogenetic characteristics, and evaluated the significance of prognostic systems. The median age was 51 years and the distribution of MDS subtypes demonstrated a markedly low incidence of MDS with deletion 5q (0.9%). The proportions of World Health Organization (WHO) categories differed according to patient age group. Refractory anemia with excess blasts-2 demonstrated the most significant trend toward increased frequency with advancing age. The incidence of abnormal karyotypes in our study was comparable to a previous study (50.2%), although with different patterns. The most frequent cytogenetic abnormality was +8 (34.5% of patients with abnormality), followed by 1q+ (17.2%), 5q− (15.5%), and 20q− (12.9%). Majority of +8, 1q+, −5/5q− and −7/7q− cases combined with additional cytogenetic abnormalities (60.0%, 75.0%, 88.5% and 100%, respectively). The median survival time was 49.5 months and 13.8% patients developed acute leukemia. WHO Prognostic Scoring System (WPSS) and age group were significant factors associated with overall survival. Otherwise, International Prognostic Scoring System was not included in the model. These results demonstrated the different cytogenetic features in Korean MDS patients compared to those of Western country. In addition, WPSS and age group are applicable to our patients as an effective and reliable prognostic model.

Cytogenetic aberrations and the development of uterine leiomyomata

This study was conducted to define the cytogenetically critical regions of uterine leiomyomata, hoping to demonstrate the presence of possible genes involved in their evolution. It was carried out on 25 randomly selected uterine leiomyoma specimens obtained from 16 patients during hysterectomy or myomectomy operations. Successful tissue culture and karyotyping were performed in 19 specimens. There was no correlation between patient age, gravidity, or presenting symptom and the presence of chromosomal abnormality. A significant correlation was found between short culture turnaround time and the occurrence of chromosomal abnormality. Abnormal clonal karyotypes were present in 6 specimens, non-clonal abnormalities in 4 specimens and normal karyotypes were found in 9 specimens. Myomas with cross section >4 cm showed an increased incidence of abnormal karyotypes and a statistically significant higher incidence of clonal abnormalities. On the other hand, submucous myomas presented fewer clonal abnormalities than did intramural or subserosal myomas. Clonal chromosomal abnormalities involved 5 different chromosomes (2, 7, 8, 12, 22), which indicate genetic heterogeneity of such benign tumors and the need of molecular cytogenetic studies or molecular studies to characterize possible candidate genes at specific chromosomal breakpoints.

FISH Reveals Abnormalities of Unsuspected Regions in Chromosomally Normal De Novo Myelodysplastic Syndromes (MDS).

Abstract 2599Poster Board II-575In de novo MDS the chromosomal pattern is a mandatory step for an accurate diagnosis, predicts overall survival (OS) and the risk of MDS/AML evolution, guides therapeutic decisions. However, conventional cytogenetics (CC) studies show a normal un-informative chromosomal pattern in about half of MDS patients, especially in low-risk disease. FISH with probes pinpointing the chromosomal regions most frequently affected in MDS can increase the incidence of abnormal karyotypes up to 60%, but the percentage of normal karyotypes remains high and makes the search of novel cytogenetic/molecular markers a urgent need. A fundamental contribution to overcome CC and FISH shortcomings, has been recently provided by array CGH (aCGH) studies which have revealed that, independently of the cytogenetic pattern, MDS patients may harbour novel abnormalities involving unsuspected chromosomal regions.Based on this assumption, we decided to investigate whether FISH with probes already employed in aCGH studies can truly unmask cryptic lesions in chromosomally normal MDS patients, whether these defects are either chromosomal gains/losses or balanced rearrangements and whether these chromosomal abnormalities influence OS and disease evolution. FISH analyses were carried out in thirty-five patients examined between January 2005 and June 2008. There were thirteen females and twenty-two males, whose median age was 66 years (range 24–78). According to WHO classification, 6 patients were classified as RA, 13 as RAEB-1 and 16 as RAEB-2. According to IPSS score, 7 patients were considered low-risk, 14 intermediate-1 risk and 14 intermediate-2 risk. Median follow-up was nine months (range 1–46). At the time of the analyses no patients has died; 6 have progressed to RAEB-2 and 3 to AML. Probes for FISH analysis were chosen following two criteria: the frequency of their involvement in chromosomal abnormalities identified by aCGH studies and their Mb position on Human Mar. 2003 assembly according to the UCSC genome browser. All probes, obtained from BACPAC Resources Center at C.H.O.R.I. (Oakland, USA), were labelled and applied as previously reported. The following probes were applied: RP11-912d8 (19q13.2); RP11-196p12 (17q11.2); RP11-269c4 (14q12); RP11-351o1 (10q21.3); RP11-144g6 (10q11.2); RP11-122a11 (7q34); RP11-951k18 (5q13.1); RP11-100m20 (4p14); RP11-544h14 (2q33). The cut-off values for interphase FISH (i-FISH) were obtained from the analysis of 300 nuclei from ten normal samples and were fixed at 10%. An abnormal FISH pattern was revealed in eighteen patients (51.4%). It was observed in 3/6 RA patients, in 7/13 RAEB-1 and in 8/16 RAEB-2 and in 2/7 IPSS low-risk, in 7/14 intermediate-1 risk and in 9/14 intermediate-2 risk MDS patients. Seven presented a 19q13.2 deletion, three a 14q12 deletion, four an amplification of band 4p14, two a defect of band 10q21.3, two a potential amplification and one a deletion of band 10q11.2, two a deletion of band 5q13.1 and one a deletion of band 17q11.2. Cryptic defects were also revealed in six of the nine patients who experienced disease evolution on FISH analyses. This event occurred in 2/3 RA, in 2/7 RAEB-1 and in 2/8 RAEB-2 patients with an abnormal FISH pattern. Despite these data, the prognostic significance of an abnormal FISH pattern needs to be assessed on additional patients.In conclusion, our data show that i) FISH can truly reveal novel lesions involving unsuspected chromosomal regions in 51% of MDS patients with a normal karyotype; ii) most of these lesions consist of chromosomal gains/losses; iii) an abnormal FISH pattern seems to correlate with disease progression, but this correlation needs to be tested on additional patients. Disclosures:No relevant conflicts of interest to declare.

Genetic defect in Chinese azoospermic patients and their relationship with reproductive hormones

To investigate the incidence of abnormal karyotypes and Y chromosome microdeletion in Chinese men with azoospermia, and the relationship with reproductive hormones. Four hundred and eighty nine cases of azoospermic patients and 20 fertile men were studied. Karyotypes and Y chromosome microdeletion were analyzed by G-banding and mutiplex polymerase chain reaction, respectively. Chemiluminescene immunoassay technique was applied to measure the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), and prolactine (PRL). Chromosome abnormalities were found in 102 out of 489 azoospermic patients (20.86%), among them 86 (84.31%) cases had sex chromosome abnormalities, with 73 cases being Klinefelter syndrome. Y chromosome microdeletions were detected in 58 (11.86%) cases out of the 489 patients, and deletion of the AZFc region was the leading group (63.8% of all deletions), followed by AZFbc (19.0%), AZFabc (10.3%), AZFb or AZFa (3.4%). FSH, LH levels were significantly increased and T level was decreased in azoospermic patients compared with the fertile men group (P<0.01). Furthermore, in the azoospermic patients with Klinefelter syndrome or AZFabc microdeletions, FSH and LH levels were increased more significantly, and were statistically different from azoospermic patients with normal karotype or without Y chromosome microdeletion (P<0.05). In the Chinese men with azoospermia, the incidence of abnormal karyotype and Y chromosome microdeletion were similar to those described previously in other populations. In azoospermia with Klinefelter syndrome or AZFabc microdeletions, FSH and LH levels increased markedly indicating the protracted stimulation of gonadotrophs due to lack of androgen feedback.

Impact of cytogenetic abnormalities on the management of skull base chordomas

Cytogenetic studies of chordomas are scarce and show multiple changes involving different chromosomes. These abnormalities are implicated in the pathogenesis of chordoma, but the clinical significance of these changes is yet to be determined. In this study, the authors discuss the cytogenetic changes in a large series of skull base chordomas with long-term follow-up and focus on the impact of these changes on the prognosis, progression, and management of the disease. The karyotypes of chordomas in 64 patients (36 men and 28 women) were studied in relation to survival and recurrence or progression over a mean follow-up period of 48 +/- 37.5 months. The standard G-banding technique was used for karyotype analysis. Statistical analysis was performed with the Fisher exact test and ORs, and Kaplan-Meier curves were generated for survival and recurrence/progression of disease. Seventy-four percent of de novo chordomas had normal karyotypes and a 3% recurrence rate; there was a 45% recurrence rate in de novo tumors with abnormal karyotypes (p < 0.01). Recurrent tumors were associated with a high incidence of abnormal karyotype (75%). The OR for recurrence in lesions with an abnormal versus a normal karyotype was 12. Aberrations in chromosomes 3, 4, 12, 13, and 14 were associated with frequent recurrence and decreased survival time. Ninety-five percent of cases with progression involved chromosome 3 and/or 13. The median survival time was 4 months when both of these chromosomes had aberrations (p = 0.02). Chordomas with normal karyotypes were associated with a low rate of recurrence and a long patient survival, and recurrent chordomas were associated with an abnormal karyotype, disease progression, and poor survival. De novo chordomas with normal karyotypes may be amenable to radical resection and adjunctive proton beam therapy. Recurrent and de novo chordomas with abnormal karyotypes were associated with complex cytogenetic abnormalities and a poor prognosis, particularly in the presence of aberrations underlying tumor progression in chromosomes 3, 4, 12, 13, and 14.

Twenty years of human cytogenetics

Human cytogenetics has undergone an immense development during the past twenty years. The number of human individuals karyotyped now amounts to some two million. The incidence of abnormal karyotypes may be estimated to 15% of all human zygotes, 50% of abortuses and 0.5% of unselected newborns. In contrast to the mouse, in which all fetuses with unbalanced translocation karyotypes nearly always die, many such individuals are live-horn in man. The study of sex chromosome aneuploidy revealed the role of the Y chromosome in sex determination and aided the discovery of the inactivation of one of the X chromosomes in female somatic cells. The chromosome handing techniques, first developed around 1970, improved enormously the resolution in structural chromosome identification. Only two phenomena, wholly new to cytogenetics, have been discovered during the period: centromeric inactivation and fragile chromosome sites. Other important developments have been the analysis of karyotypic evolution in neoplasms, chromosome responses to mutagenic agents and meiotic events related to male infertility. Looking forward, two areas of research seem especially urgent: chromosome studies in very early embryos and systematic registration on a world scale of karyotypes from prenatal diagnosis. Other promising areas include the organisation of the human genome, the H-Y antigen, and the ancient problem of meiosis.

Isolated choroid plexus cyst or echogenic cardiac focus on prenatal ultrasound: is genetic amniocentesis indicated?

The purpose of this study was to determine whether or not genetic amniocentesis is warranted when isolated choroid plexus cysts (CPC) or echogenic cardiac foci (EF) are noted on prenatal ultrasound. We performed a retrospective analysis on patients from our perinatal database. All obstetric patients with CPC or EF noted on second-trimester perinatology ultrasound from April, 1998 to November, 2004 were included. Information regarding ultrasound findings and neonatal outcome were analyzed. During the study period, 515 patients with CPC or EF were evaluated. Of these, 429 (83.3%) had isolated CPC or EF and 86 (16.7%) had additional risk factors. The incidence of abnormal karyotype was 0 versus 2.3%, respectively (P = .03). The additional risk factors considered were: advanced maternal age, abnormal serum triple marker screening, and/or other abnormal ultrasound findings. Furthermore, during the study period there were 20,122 live births and 27 (0.1%) cases of aneuploidy diagnosed postnatally. Of these, none had isolated CPC or EF on prenatal ultrasound. CPC or EF noted on prenatal ultrasound warrants referral for careful consultative ultrasound evaluation. In the absence of other risk factors, however, genetic amniocentesis for isolated CPC or EF does not appear to be necessary.