Type Of Translocation Research Articles

Are ovarian responses and the number of transferable embryos different in females and partners of male balanced translocation carriers?

To compare ovarian response and the number of transferable embryos between women with balanced autosomal translocations and women whose partners carry the translocation (control group). To investigate the predictive value of metaphase II (MII) oocyte number and biopsied embryo number for gaining at lowest one transferable embryo. We retrospectively analyzed 1942 preimplantation genetic testing for structural rearrangements (PGT-SR) cycles of 1505 balanced autosomal translocation couples over 8years. All cycles were divided into two subgroups: Robertsonian and reciprocal translocations (ROBT and ReBT). Receiver operator characteristic (ROC) curves were plotted to ascertain a cutoff of MII oocytes and biopsied embryos as predictors of gaining at lowest one transferable embryo. There were no statistical differences in baseline features or ovarian response indicators regarding the number of retrieved/MII oocytes, E2 level on the day of HCG, and ovarian sensitivity index (OSI) between women with balanced autosomal translocations and control group (P > 0.05). A decreased number of transferable embryos were found in women with balanced autosomal translocations regardless of the type of translocation. The cutoff values for gaining at lowest one transferable embryo are 12.5 MII oocytes and 4.5 biopsied embryos, respectively. Women with balanced autosomal translocations have a normal ovarian response, but fewer transferable embryos, meaning that higher gonadotropin (Gn) doses may be required to increase transferable embryos. When fewer than 12.5 MII oocytes or 4.5 blastocysts are obtained in a PGT-SR cycle, couples should be notified that the likelihood of gaining a transferable embryo is low.

Characterization of a Wheat-Dasypyrum breviaristatum Chromosome Addition and Its Derived Progenies Carrying Novel Dasypyrum-Specific Gliadin Genes

The construction of the 28-chromosome karyotype of Dasypyrum breviaristatum was undertaken using multicolor non-denaturing fluorescent in situ hybridization (ND-FISH) and Oligo-FISH painting protocols. A novel wheat-D. breviaristatum line D2138 contained 44 chromosomes including a pair of D. breviaristatum 6VbS.2VbL translocation chromosomes. Individual F2 and F3 progenies of a cross between D2138 with wheat lines CM62, MY11 and JM22, respectively, were characterized using ND-FISH and molecular markers. A relatively high chromosome alteration rate within wheat and D. breviaristatum 6VbS and 2VbL was observed in the three progeny populations, suggesting that chromosome 6VbS.2VbL has a gametocidal-like gene. The different types of translocation and deletion lines allowed localization of D. breviaristatum-specific gliadin coding genes on sub-telomeric regions of 6VbS by PCR and acid polyacrylamide gel electrophoresis analysis. The positive effect of the D. breviaristatum 6VbS on agronomic and quality characters was also demonstrated. The new wheat-D. breviaristatum 6VbS and 2VbL translocation lines will be useful as novel germplasm for breeding purposes.

Beyond Wilms tumor: imaging findings and outcomes of rare renal tumors in children.

Compared to Wilms, non-Wilms renal tumors in children are less well understood due to their rare occurrence which limits precise definition of the typical imaging patterns. This study aims to identify distinctive imaging findings, demographic characteristics and prognosis of pediatric non-Wilms renal tumors. From January 2007 to December 2018, 207 patients with a diagnosis of primary kidney neoplasia were yielded from our radiology archive, 171 of whom were diagnosed with Wilms tumor, 4 with angiomyolipoma and one with nephrogenic rest. The remaining 31 patients with a diagnosis of primary kidney neoplasia were enrolled in this retrospective study. Imaging data, age, gender, prognosis and findings regarding follow-up were noted. Eight patients had renal cell carcinoma, seven had clear cell sarcoma, six had mesoblastic nephroma, four had rhabdoid tumor, three had desmoplastic small round cell tumor, two had cystic nephroma and one had metanephric stromal tumor. The age of diagnosis was > 8years for renal cell carcinoma and desmoplastic small round cell tumor, < 5years for rhabdoid tumor and < 7months for mesoblastic nephroma. There was no gender preference for any tumor type. The prognosis for rhabdoid tumor was extremely poor in that all the patients followed up in our institute were deceased, whereas no recurrence was found in other tumors. Translocation type renal cell carcinoma had lower T2-weighted signal intensity, mesoblastic nephroma was a predominantly cystic mass, clear cell sarcoma was generally larger at presentation and extensive amorphous calcifications were seen in desmoplastic small round cell tumor. For the differential diagnosis of pediatric non-Wilms renal tumors, age is the most important factor, followed by propensity to metastasize/aggressive behavior of the mass. Knowledge of specific imaging findings of these tumors may help to narrow the differential diagnosis.

P964: IMMUNOPHENOTYPED-SUSPENSION-MULTIPLEX FISH BY IMAGING FLOW CYTOMETRY FOR THE SIMULTANEOUS DIAGNOSIS OF THREE PIVOTAL IGH TRANSLOCATIONS IN MULTIPLE MYELOMA

Background: The cytogenetic abnormalities including t(4;14)(p16;q32), t(14;16)(q32;q23), and t(11;14)(q13;q32) are associated with the molecular profiles, clinical features, and treatment outcome in multiple myeloma (MM). Although the double-color interphase fluorescence in situ hybridization (DC-FISH) is well established to detect those translocations, the conventional method can analyze only one abnormality on each slide. Aims: To analyze multiple chromosomal abnormalities simultaneously with high sensitivity and specificity, we aimed to develop a new diagnostic modality of four-color FISH for multiple translocations in immunophenotyped cells in suspension using imaging flow cytometry (immunophenotyped-suspension-multiplex (ISM)-FISH). Methods: For the ISM-FISH, we first subjected Carnoy-fixed cells in suspension to immunostaining using a brilliant violet 421-conjugated anti-CD138 antibody. Then, we hybridized with four different FISH probes, i.e., Texas Red (TxRed)-conjugated probe for IGH, fluorescein isothiocyanate (FITC)-conjugated probe for FGFR3, Gold-conjugated probe for cyclin D1 (CCND1), and Cy5-conjugated probe for c-MAF, in suspension. Then, more than 2.5 × 104 nucleated cells for each sample were analyzed with imaging flow cytometer MI-1000 (Sysmex) by six channels: one for immunophenotyping, four for FISH and one for bright field image. In the process of imaging flowcytometric analysis, we sorted CD138-positive cell fraction, computed the distance between FISH probes using originally developed spot counting tool, and determined to be positive for translocation when the distance is under the threshold. Results: By this ISM-FISH system, we simultaneously examined three chromosomal translocations, including t(4;14), t(14;16), and t(11;14), in three MM cell lines, KMS-11, KMS-21-BM, KMS-26, and successfully detect the abnormalities. Using different proportions of transformation-positive MM cells spiked with transformation-negative leukemic cells, HL-60, ISM-FISH showed a sensitivity of less than 0.1%. Next, ISM-FISH and conventional DC-FISH were performed for bone marrow nucleated cells from 70 patients with MM or monoclonal gammopathy of undetermined significance (MGUS) and the experiments showed a promising qualitative diagnostic ability in detecting t(11;14), t(4;14), and t(14;16) of our ISM-FISH, which was more sensitive than standard DC-FISH, examining 200 interphase cells with its optimal sensitivity of up to 1.0%. Furthermore, the ISM-FISH showed a positive concordance of 83.3% and negative concordance of 97.4% using standard DC-FISH, examining 200 interphase cells. Furthermore, in three patients (4%), t(4;14) or t(11;14) were positive by ISM-FISH but negative by DC-FISH examining 200 cells. Extensive DC-FISH study examining additional 1,000 cells showed positive in these ISM-FISH-positive/DC-FISH (200cells)-negative samples, suggesting higher sensitivity of ISM-FISH than that of the standard DC-FISH. Image:Summary/Conclusion: This study developed the new diagnostic system of ISM-FISH, which enables the simultaneous diagnosis of three clinically pivotal chromosomal translocations, t(4;14), t(14;16), and t(11;14), in MGUS and MM. This system may facilitate rapid and reliable cytogenetic diagnosis and promote patient-oriented therapy according to the type of chromosomal translocation in the clinical practice setting.

A Nonimmune Hydrops Case.

A Nonimmune Hydrops Case.

A report on chromosomal translocation types in relation to male infertility

Introduction: Male infertility (MI) in about 50% of couples is constituted due to genetic, hormonal, and epigenetic factors. Almost 10% of it is contributed to genetic anomalies. Objectives: This study was undertaken in 787 males with infertility and the impacts of the type of translocations in these cases were studied in relation to MI. Materials and Methods: Five milliliters (ml) of blood were drawn from referred cases suspected with MI and were used for cytogenetic analysis with Giemsa stain following International System for Human Cytogenetic Nomenclature. Results: Of 6142 referral cases, 787 were detected with MI (787/6142; 12.8%). Forty-four translocations (44/787; 5.6%) were detected in 787 infertile men. Other chromosomal abnormalities were 21% (167/787) in them. Among all translocations, an autosome-autosomal translocations were higher in frequency (24/787; 3.1%) than Robertsonian (15/787; 1.9%) and autogonosomal translocations (5/787; 0.6%). Few translocations seemed to be rare as our knowledge is concerned. Maharashtra had high frequency of translocations followed by Delhi union territory (UT) and Gujarat (07 each) and other states. Most of the translocations were related to infertility. Seven males had primary infertility (7/44) and six with secondary type (6/44) in this study. Conclusions: These reciprocal translocations are important in causation of infertility affecting testicular spermatogenesis. Few are rare in our study. Such cases are clinically suggested for counseling before adopting assisted reproductive technologies.

Kiwi translocation review: are we releasing enough birds and to the right places?

Translocations of kiwi (Apteryx spp.) are one of the most common and growing types of conservation translocations in New Zealand. However, their outcomes remain mostly unpublished, which does not allow for sharing of lessons learnt from past developments. We reviewed 102 kiwi translocations from the 19th century until 2018, and identified factors affecting their outcome. North Island brown kiwi (A.

CYTOGENETIC AND CLINICAL DATA OF VARIANT THREE-WAY TRANSLOCATIONS T(8;V;21) IN CHILDHOOD ACUTE MYELOID LEUKEMIA

Core binding factor (CBF) leukemias represent an important prognostic group in acute myeloid leukemia (AML). The t(8;21)(q22;q22)/ RUNX1 - RUNX1T1 is one of the most frequent abnormalities in childhood AML (7–16%) and is related to a good prognosis. However, on rare occasions, an additional chromosome may be involved in this translocation, which may result in a poor clinical outcome for the patient. In this sense, the prognostic value of the RUNX1 - RUNX1T1 fusion has been widely discussed in the literature. Approximately 3–4% of AML cases with t(8;21)/ RUNX1 - RUNX1T1 occur in the context of complex rearrangements, with only a few cases reported in children (0.05–1.1%). Our aim in this work is to demonstrate the clinical and molecular data from four AML pediatric patients with variant three-way translocations t(8;V;21), characterizing in detail the extra chromosomes and fusion products. In our cohort of 146 children diagnosed with AML, we observed 22 with complex karyotypes (>3 abnormalities). To date, we detected the t(8;21) in 5/22 cases, among which 4 patients presented the involvement of a third chromosome in t(8;21), characterizing variant three-way translocations t(8;V;21). To characterize the patient's karyotypes, G-banding, FISH, and high-resolution molecular cytogenetics experiments (PCP, WCP, M-FISH, and MCB) were performed on bone marrow and/or peripheral blood cells under standard protocols. Regarding the mechanism of this type of translocation, Downing et al. (1993) and Tanaka et al. (2012) reported that there are at least two stages for the formation of such complex variants. The region 21(q22) (harboring the RUNX1 gene) translocates to the long arm of chromosome 8, while region 8q22 (harboring the RUNX1T1 gene) translocates to a third chromosome. Interestingly, in our 4 cases, t(8;V;21) demonstrated the same biological behavior in the rearrangement as the other cases reported in the literature. Although, unlike the cases previously reported in the literature, the karyotypes characterized in our study were cryptic, reaffirming the importance of an accurate diagnosis of RUNX1 - RUNX1T1 fusion products. With our approach by molecular cytogenetic techniques, we were able to precisely define the breakpoints of the three-way translocations, which will be of importance for future studies, investigating putative genes with impact on the genesis of pediatric CBF leukemias.

What is the threshold of mature oocytes to obtain at least one healthy transferable cleavage-stage embryo after preimplantation genetic testing for fragile X syndrome?

What are the chances of obtaining a healthy transferable cleavage-stage embryo according to the number of mature oocytes in fragile X mental retardation 1 (FMR1)-mutated or premutated females undergoing preimplantation genetic testing (PGT)? In our population, a cycle with seven or more mature oocytes has an 83% chance of obtaining one or more healthy embryos. PGT may be an option to achieve a pregnancy with a healthy baby for FMR1 mutation carriers. In addition, FMR1 premutation is associated with a higher risk of diminished ovarian reserve and premature ovarian failure. The number of metaphase II (MII) oocytes needed to allow the transfer of a healthy embryo following PGT has never been investigated. The study is a monocentric retrospective observational study carried out from January 2006 to January 2020 that is associated with a case-control study and that analyzes 38 FMR1 mutation female carriers who are candidates for PGT; 16 carried the FMR1 premutation and 22 had the full FMR1 mutation. A total of 95 controlled ovarian stimulation (COS) cycles for PGT for fragile X syndrome were analyzed, 49 in premutated patients and 46 in fully mutated women. Only patients aged ≤38 years with anti-Müllerian hormone (AMH) >1 ng/ml and antral follicle count (AFC) >10 follicles were eligible for the PGT procedure. Each COS cycle of the FMR1-PGT group was matched with the COS cycles of partners of males carrying any type of translocation (ratio 1:3). Conditional logistic regression was performed to compare the COS outcomes. We then estimated the number of mature oocytes needed to obtain at least one healthy embryo after PGT using receiver operating characteristic curve analysis. Overall, in the FMR1-PGT group, the median number of retrieved and mature oocytes per cycle was 11 (interquartile range 7-15) and 9 (6-12), respectively. The COS outcomes of FMR1 premutation or full mutation female carriers were not altered compared with the matched COS cycles in partners of males carrying a balanced translocation in their karyotype. Among the 6 (4-10) Day 3 embryos obtained in the FMR1-PGT group, a median number of 3 (1-6) embryos were morphologically eligible for biopsy, leading to 1 (1-3) healthy embryo. A cutoff value of seven MII oocytes yielded a sensitivity of 82% and a specificity of 61% of having at least one healthy embryo, whereas a cutoff value of 10 MII oocytes led to a specificity of 85% and improved positive predictive value. This study is retrospective, analyzing a limited number of cycles. Moreover, the patients who were included in a fresh PGT cycle were selected on ovarian reserve parameters and show high values in ovarian reserve tests. This information could influence our conclusion. The results relate only to the target population of this study, with a correct ovarian reserve of AMH >1 and AFC >10. However, the information provided herein extends knowledge about the current state of COS for FMR1 mutation carriers in order to provide patients with proper counseling regarding the optimal number of oocytes needed to have a chance of transferring an unaffected embryo following PGT. None. N/A.

Clinical and Neurological Changes in Children with Down Syndrome Based on The Cytogenetic Profile

Down syndrome is the most common chromosomal pathology. It occurs when another chromosome appears in the 21st pair as a result of a random mutation. Often, children with Down syndrome (DS) and related disorders have some neurological problems, severe forms of stereotyped behavior. The purpose of this article was to study the neurological conditions of children with DS. Clinical, neurological, studies were performed in 120 children (75 boys, 45 girls) with DS. It was found that in children with trisomy, neurological deficits in the form of speech disorders, fine motor skills of the hand, disorders of the coordination sphere and autonomic dysregulation are more severe than in children with mosaic and translocation types.

Killing them softly: a review on snake translocation and an Australian case study

Human-wildlife conflicts with ‘nuisance’ snakes are becoming more frequent around the world as urbanisation continues to encroach on remaining habitats. In an attempt to mitigate this issue, snakes are often translocated in an uncontrolled fashion, with little to no conservation value. To determine the most appropriate methods of translocation we reviewed the available primary literature on studies performing translocations of snakes. We found two types of translocation: long and short-distance. Based on the welfare of the animals involved and difficulty of achieving success with long-distance translocations, we deduced that short-distance translocations are the most favourable. We also reviewed the literature on a third method - repatriating wild populations of snakes with captive-bred or captive-reared individuals, the results of which were very similar to those of long-distance translocations. In conjunction with a mark recapture study carried out by snake catchers in Darwin, Australia, we use our findings to make suggestions on the most appropriate course of action for the mitigation-based snake catching activities in Australia. The difficulty of ensuring successful outcomes for long distance translocations along with a high mortality rate meant we cannot suggest this as an appropriate method for managing ‘nuisance’ snakes. Instead, we argue that short distance translocations are the most suitable for the welfare of the snakes involved. Nevertheless, no outcome will be more favourable for the snakes than to be simply released within their home range accompanied by a change in attitude of the general public towards a willingness to coexist. Although we focus primarily on Australia our suggested framework can be applied in any country where there is conflict with snakes. Furthermore, should our suggestions be implemented, they are merely a temporary solution to an ongoing problem and we are in desperate need for further research to devise a long-term management plan.

Analysis of barley mutants ert-c.1 and ert-d.7 reveals two loci with additive effect on plant architecture

Main conclusionBoth mutant ert-c.1 and ert-d.7 carry T2-T3 translocations in the Ert-c gene. Principal coordinate analyses revealed the translocation types and translocation breakpoints. Mutant ert-d.7 is an Ert-cErt-d double mutant.Mutations in the Ert-c and Ert-d loci are among the most common barley mutations affecting plant architecture. The mutants have various degrees of erect and compact spikes, often accompanied with short and stiff culms. In the current study, complementation tests, linkage mapping, principal coordinate analyses and fine mapping were conducted. We conclude that the original ert-d.7 mutant does not only carry an ert-d mutation but also an ert-c mutation. Combined, mutations in Ert-c and Ert-d cause a pyramid-dense spike phenotype, whereas mutations in only Ert-c or Ert-d give a pyramid and dense phenotype, respectively. Associations between the Ert-c gene and T2-T3 translocations were detected in both mutant ert-c.1 and ert-d.7. Different genetic association patterns indicate different translocation breakpoints in these two mutants. Principal coordinate analysis based on genetic distance and screening of recombinants from all four ends of polymorphic regions was an efficient way to narrow down the region of interest in translocation-involved populations. The Ert-c gene was mapped to the marker interval of 2_0801to1_0224 on 3HL near the centromere. The results illuminate a complex connection between two single genes having additive effects on barley spike architecture and will facilitate the identification of the Ert-c and Ert-d genes.

Cytogenetic events in the endosperm of amphiploid Avena magna\u2009\xd7\u2009A. longiglumis

This study analysed cytogenetic events occurring in the syncytial endosperm of the Avena magna H. C. Murphy & Terrell × Avena longiglumis Durieu amphiploid, which is a product of two wild species having different genomes. Selection through the elimination of chromosomes and their fragments, including those translocated, decreased the level of ploidy in the endosperm below the expected 3n, leading to the modal number close to 2n. During intergenomic translocations, fragments of the heterochromatin-rich C-genome were transferred to the D and Al genomes. Terminal and non-reciprocal exchanges dominated, whereas other types of translocations, including microexchanges, were less common. Using two probes and by counterstaining with DAPI, the A. longiglumis and the rare exchanges between the D and Al genomes were detected by GISH. The large discontinuity in the probe labelling in the C chromosomes demonstrated inequality in the distribution of repetitive sequences along the chromosome and probable intragenomic rearrangements. In the nucleus, the spatial arrangement of genomes was non-random and showed a sectorial-concentric pattern, which can vary during the cell cycle, especially in the less stable tissue like the hybrid endosperm.

Associated costs of mitigation-driven translocation in small lizards

Abstract Mitigation-driven translocations represent an increasingly common management solution to reduce animal mortality and habitat loss caused by human development. Although they currently outnumber other translocation types, there is a lack of scientific approaches to evaluate the outcome of this management tool. We designed an experimental translocation with two groups of translocated males and two of control males of a small (6-14 g) lizard (totaling 120 individuals). Our results suggest that translocated individuals covered longer distances (53 vs. 18 m) from their respective release points in one month (on average), although this distance diminished over time. Displacing longer distances was associated with a body condition impoverishment and an increase in parasitization by ectoparasites. To the best of our knowledge, this is the first study that finds a positive relationship between covering longer distances and an increase in the number of mites. This was also explained by the initial mite load that lizards had, suggesting that controlling the infestation by mites is energetically demanding for lizards, being traded by locomotor activity. At least for those individuals in poorer body condition, we recommend the implementation of soft release (gradually accustoming individuals to their new environment by previously releasing them into controlled conditions) and deparasitization before accomplishing a mitigation-driven translocation.

A Critical Review on the Impacts of Nanoplastics and Microplastics on Aquatic and Terrestrial Photosynthetic Organisms.

Microplastic and nanoplastic contamination is widespread and affects aquatic and terrestrial ecosystems. Photosynthetic organisms are present in both media, they are primary producers, sink for CO2 , and they represent a major point of entry in the food chain. Here, the current knowledge on the fate and impacts of microplastics and nanoplastics in interaction with these organisms is reviewed. As a general trend, plastic characteristics (smaller size and positive charge) play a crucial role in their toxicity toward photosynthetic organisms. Plastic leachates (containing additives) also represent a major source of toxicity, and some harmful compounds such as phthalate esters are shown to accumulate in plants and generate a risk for the consumers. Adsorption of plastic particles is evidenced for each type of photosynthetic organism, and uptake and translocation in terrestrial plants is evidenced for nanoplastics, leading to concerns for trophic chain contamination. The available techniques for the detection of microplastics and nanoplastics and their secondary products in biological samples and media are also listed. Finally, the current gaps of knowledge, specific challenges, and future research directions are also discussed.

Envelopment by endothelial cells initiates translocation of avian primordial germ cell into vascular tissue.

In avian species, primordial germ cells (PGCs) migrate to the gonadal primordium through the vascular system. Because this mode of migration is reminiscent of cancer metastasis, it would be useful to elucidate the mechanisms underlying PGC migration via the bloodstream. Here, we sought to determine when, where, and how PGCs enter the vascular network by double visualization of PGCs and endothelial cells (ECs) in tie1:H2B-eYFP transgenic quails. In the left and right lateral germinal crescent regions corresponding to the anterior-most area vasculosa, more than 60% of PGCs were enveloped by differentiating ECs forming blood islands prior to vascular network formation. Cell morphology analysis suggested that the PGC-EC interaction was instructed by differentiating ECs. At a later developmental stage, ECs anastomosed to form a vascular network with a lumen that retained PGCs within it. As a consequence, many PGCs localized within the luminal space of the mature vascular network at later stages. Our findings demonstrate that the major type of avian PGC translocation into vascular tissue is not a typical intravasation, as performed by types of metastatic cancer cells, but rather a passive translocation (envelopment) mediated by differentiating ECs during early vasculogenesis.

P73.02 The Landscape of FGFR Alteration in Chinese Patients with Lung Cancer

Fibroblast growth factor (FGF) family being part of the receptor tyrosine kinase (RTK) families exerts their functions through four highly conserved tyrosine kinase receptors (including FGFR1, FGFR2, FGFR3 or FGFR4). Aberrant activation of the FGFR signaling pathway by genetic alteration (GA) seems to be mainly responsible for the neoplastic development in many cancers including non-small cell lung cancer (NSCLC). These make FGFR family genes to be highly potential therapy target in cancers and several inhibitors targeting FGFR have demonstrated clinical benefit in cancer patients, such as Erdafitinib in metastatic urothelial cancers. However, the landscape of FGFR genes in Chinese patients with lung cancer has not been well understood and the correlation between FGFR genetic alterations and immune checkpoint inhibitors (ICIs) response in NSCLC remains unclear. Formalin-fixed, paraffin-embedded (FFPE) tumor samples were collected from 6275 Chinese patients with lung cancer and subjected to a clinical-grade next-generation sequencing (NGS)-based 450 gene panel test from December 2017 to January 2019. GAs including single nucleotide variations, short and long insertions/deletions, copy number variations, and gene rearrangements were assessed. Genomic data and ICIs treatment outcome of 2 cohorts of NSCLC patients were derived from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) databases. Genomic alterations (GAs) of FGFR1-4 were detected in 5.3% of patients with lung cancer in the OrigiMed database, including 2.5% FGFR1 GAs, 1.2% FGFR4 GAs, 0.9% FGFR3 GAs, and 0.9% FGFR2 GAs. The frequency of FGFR alteration was highest in squamous cell lung carcinoma (15.9%), followed by small cell lung cancer (6.6%) and lung adenocarcinoma (3.6%). Amplification was the most common type of FGFR variation, which accounted for 45.9% of all FGFR GAs, followed by substitution/indels (45%), fusion/rearrangements (7.8%) and truncations (1.3%). FGFR3-TACC3 was the most common type of FGFR translocations (34.6%) and SNTG1-FGFR1, CADPS2-FGFR1 and UGP2-FGFR2 were novel types of FGFR fusion/rearrangement identified in our cohort. The most common co-alterations associated with FGFR alterations were TP53 (76.9%), EGFR (33.3%), LRP1B (26.1%), CDKN2A (20%) and PIK3CA (19.5%). Compared with wild-type (WT), FGFR1-4 GAs were associated with a significantly higher tumor mutational burden (TMB) (10 vs. 4.6 muts/Mb, respectively, p<0.001). Survival analysis from 2 independent cohorts confirmed that FGFR4 GAs but not FGFR1-3 were associated with longer progression free survival (PFS) (13.17 months vs 3.17 months, respectively, p=0.025) and higher proportion of durable clinical benefit (DCB) (80% vs 29.3%, respectively, p=0.03) of immune checkpoint inhibitors treatments. Furthermore, FGFR4 GAs were an independent risk factor of PFS (HR: 0.22, 95%CI: 0.055-0.92, p=0.037) and overall survival (OS) (HR: 0.23, 95%CI: 0.057-0.92, p=0.038). FGFR-alterations were found in 5.3% of Chinese patients with lung cancers. Lung cancer patients with FGFR alterations were associated with an increased TMB but only those harboring FGFR4 GAs might experience favorable response to ICIs. This suggests that GAs of FGFR4 may have implications as a biomarker for guiding ICI treatment.

The Effectiveness of Next-Generation Sequencing-Based Preimplantation Genetic Testing for Balanced Translocation Couples

The purpose of this study was to evaluate the effectiveness of next-generation sequencing (NGS)-based preimplantation genetic testing (PGT) for balanced translocation carriers to identify normal/balanced blastocysts and to measure pregnancy outcomes following euploid embryo transfer. We enrolled 75 couples with a balanced translocation who underwent 83 PGT cycles (58 cycles for carriers with reciprocal translocations and 25 cycles for carriers with Robertsonian translocations) and 388 blastocysts were diagnosed. Moreover, we transferred single euploid blastocysts through frozen embryo transfer and calculated the biochemical pregnancy, clinical pregnancy, miscarriage, and ongoing pregnancy rates per embryo transfer cycle. Despite a mean maternal age of 29.8 years and mean of 4.34 embryos biopsied, there was a 32.8% chance of recording no chromosomally normal/balanced embryos for reciprocal translocation carriers. The proportion of normal/balanced embryos was significantly higher (44.1 vs. 27.8%) in Robertsonian translocation carriers than in reciprocal translocation carriers. Female carriers had a significantly lower (23.3 vs. 42.4%, 34.7 vs. 54.7%, respectively) percentage of normal/balanced embryos than male carriers, regardless of the translocation. After transfering single blastocysts, we obtained a 64.4% clinical pregnancy rate per transfer, and the clinical miscarriage rate was 5.7%. Amniocentesis results showed that all karyotypes of the fetuses were consistent with PGT results. The clinical outcomes are probably not influenced by the type of translocation, maternal age, and blastocyst morphology following the transfer of euploid blastocysts. Therefore, we conclude that NGS-based PGT is an efficient method for analyzing balanced translocation carriers, and aneuploidy screening had good clinical outcomes.

Meiotic Heterogeneity of Trivalent Structure and Interchromosomal Effect in Blastocysts With Robertsonian Translocations.

BackgroundRobertsonian translocations are common structural rearrangements and confer an increased genetic reproductive risk due to the formation of trivalent structure during meiosis. Studies on trivalent structure show meiotic heterogeneity between different translocation carriers, although the factors causing heterogeneity have not been well elaborated in blastocysts. It is also not yet known whether interchromosomal effect (ICE) phenomenon occurs in comparison with suitable non-translocation control patients. Herein, we aimed to evaluate the factors that cause meiotic heterogeneity of trivalent structure and the ICE phenomenon.MethodsWe designed a retrospective study, comprising 217 Robertsonian translocation carriers and 134 patients with the risk of transmitting monogenic inherited disorders (RTMIDs) that underwent preimplantation genetic testing (PGT). Data was collected between March 2014 and December 2019. The segregation products of trivalent structure were analyzed based on the carrier’s gender, age and translocation type. In addition, to analyze ICE phenomenon, aneuploidy abnormalities of non-translocation chromosomes from Robertsonian translocation carriers were compared with those from patients with RTMIDs.ResultsWe found that the percentage of male carriers with alternate segregation pattern was significantly higher [P < 0.001, odds ratio (OR) = 2.95] than that in female carriers, while the percentage of adjacent segregation pattern was lower (P < 0.001, OR = 0.33). By contrast, no difference was observed between young and older carriers when performing stratified analysis by age. Furthermore, segregation pattern was associated with the D;G chromosomes involved in Robertsonian translocation: the rate of alternate segregation pattern in Rob(13;14) carriers was significantly higher (P = 0.010, OR = 1.74) than that in Rob(14;21) carriers, whereas the rate of adjacent segregation pattern was lower (P = 0.032, OR = 0.63). Moreover, the results revealed that the trivalent structure could significantly increase the frequencies of chromosome aneuploidies 1.30 times in Robertsonian translocation carriers compared with patients with RTMIDs (P = 0.026), especially for the male and young subgroups (P = 0.030, OR = 1.35 and P = 0.012, OR = 1.40), while the mosaic aneuploidy abnormalities presented no statistical difference.ConclusionsOur study demonstrated that meiotic segregation heterogeneity of trivalent structure is associated with the carrier’s gender and translocation type, and it is independent of carrier’s age. ICE phenomenon exists during meiosis and then increases the frequencies of additional chromosome abnormalities.

Characteristics and outcome of pediatric renal cell carcinoma patients registered in the International Society of Pediatric Oncology (SIOP) 93-01, 2001 and UK-IMPORT database: A report of the SIOP-Renal Tumor Study Group.

In children, renal cell carcinoma (RCC) is rare. This study is the first report of pediatric patients with RCC registered by the International Society of Pediatric Oncology‐Renal Tumor Study Group (SIOP‐RTSG). Pediatric patients with histologically confirmed RCC, registered in SIOP 93‐01, 2001 and UK‐IMPORT databases, were included. Event‐free survival (EFS) and overall survival (OS) were analyzed using the Kaplan‐Meier method. Between 1993 and 2019, 122 pediatric patients with RCC were registered. Available detailed data (n = 111) revealed 56 localized, 30 regionally advanced, 25 metastatic and no bilateral cases. Histological classification according to World Health Organization 2004, including immunohistochemical and molecular testing for transcription factor E3 (TFE3) and/or EB (TFEB) translocation, was available for 65/122 patients. In this group, the most common histological subtypes were translocation type RCC (MiT‐RCC) (36/64, 56.3%), papillary type (19/64, 29.7%) and clear cell type (4/64, 6.3%). One histological subtype was not reported. In the remaining 57 patients, translocation testing could not be performed, or TFE‐cytogenetics and/or immunohistochemistry results were missing. In this group, the most common RCC histological subtypes were papillary type (21/47, 44.7%) and clear cell type (11/47, 23.4%). Ten histological subtypes were not reported. Estimated 5‐year (5y) EFS and 5y OS of the total group was 70.5% (95% CI = 61.7%‐80.6%) and 84.5% (95% CI = 77.5%‐92.2%), respectively. Estimated 5y OS for localized, regionally advanced, and metastatic disease was 96.8%, 92.3%, and 45.6%, respectively. In conclusion, the registered pediatric patients with RCC showed a reasonable outcome. Survival was substantially lower for patients with metastatic disease. This descriptive study stresses the importance of full, prospective registration including TFE‐testing.