Use Of Single Nucleotide Polymorphism Arrays Research Articles

Refined cytogenetic IPSS-R evaluation by the use of SNP array in a cohort of 290 MDS patients.

Genetic testing plays a central role in myelodysplastic neoplasms (MDS) diagnosis, prognosis, and therapeutic decisions. The widely applied cytogenetic revised international prognostic scoring system (IPSS-R) was based on chromosome banding analysis (CBA). However, subsequently developed genetic methodologies, such as single nucleotide polymorphism (SNP) array, demonstrated to be a valid alternative test for MDS. SNP array is, in fact, able to detect the majority of MDS-associated cytogenetic aberrations, by providing further genomic information due to its higher resolution. In this study, 290 samples from individuals with a confirmed or suspected diagnosis of MDS were tested by both CBA and SNP array, in order to evaluate and compare their cytogenetic IPSS-R score in the largest MDS cohort reported so far. A concordant or better refined cytogenetic IPSS-R array-based score was obtained for 95% of cases (277). Therefore, this study confirms the effective applicability of SNP array toward the cytogenetic IPSS-R evaluation and consequently, toward the molecular international prognostic scoring system for MDS (IPSS-M) assessment, which ensures an improved MDS risk stratification refinement. Considering the advent of additional genetic technologies interrogating the whole genome with increased resolutions, counting cytogenetic abnormalities based on their size may result in a simplistic approach. On the contrary, assessing overall genomic complexity may provide additional crucial information. Independently of the technology used, genetic results should indeed aim at ensuring a highly refined stratification for MDS patients.

Combining metaphase cytogenetics with single nucleotide polymorphism arrays can improve the diagnostic yield and identify prognosis more precisely in myelodysplastic syndromes

Background Myelodysplastic syndromes (MDS) encompass a group of heterogeneous haematopoietic stem cell malignancies characterised by ineffective haematopoiesis, cytological aberrations, and a propensity for progression to acute myeloid leukaemia. Diagnosis and disease prognostic stratification are much based on genomic abnormalities. The traditional metaphase cytogenetics analysis (MC) can detect about 40–60% aberrations. Single-nucleotide polymorphism arrays (SNP-A) karyotyping can detect copy number variations with a higher resolution and has a unique advantage in detection of copy number neutral loss of heterozygosity (CN-LOH). Combining these two methods may improve the diagnostic efficiency and accuracy for MDS. Methods We retrospectively analysed the data of 110 MDS patients diagnosed from January 2012 to December 2019 to compare the detection yield of chromosomal abnormalities by MC with by SNP-A, and the relationship between chromosomal abnormalities and prognosis. Results Our results showed that SNP-A improved the detection yield of chromosomal aberrations compared with MC (74.5 vs. 55.5%, p < .001). In addition, the positive yield could be further improved by combining MC with SNP-A to 77.3%, compared with MC alone. Univariate analysis showed that age >65 years, bone marrow blasts ≥5%, with acquired CN-LOH, new aberrations detected by SNP-A, TGA value > the median (81.435 Mb), higher risk by IPSS-R-MC, higher risk by IPSS-R-SNP-A all had poorer prognosis. More critically, multivariable analysis showed that age >65 years and higher risk by IPSS-R-SNP-A were independent predictors of inferior OS in MDS patients. Conclusion The combination of MC and SNP-A based karyotyping can further improve the diagnostic yield and provide more precise prognostic stratification in MDS patients. However, SNP-A may not completely replace MC because of its inability to detect balanced translocation and to detect different clones. From a practical point of view, we recommend the concurrent use of SNP-A and MC in the initial karyotypic evaluation for MDS patients on diagnosis and prognosis stratification. KEY MESSAGES SNP-A based karyotyping can further improve the MDS diagnostic yield and provide more precise prognostic stratification in MDS patients. Acquired CN-LOH is a characteristic chromosomal aberration of MDS, which should be integrated to the diagnostic project of MDS. The concurrent use of SNP-A and MC in the initial karyotypic evaluation for MDS patients can be recommended.

From Benign Inflammatory Dermatosis to Cutaneous Lymphoma. DNA Copy Number Imbalances in Mycosis Fungoides versus Large Plaque Parapsoriasis.

Background and Objectives: Mycosis fungoides (MF) and large plaque parapsoriasis (LPP) evolution provide intriguing data and are the cause of numerous debates. The diagnosis of MF and LPP is associated with confusion and imprecise definition. Copy number alterations (CNAs) may play an essential role in the genesis of cancer out of genes expression dysregulation. Objectives: Due to the heterogeneity of MF and LPP and the scarcity of the cases, there are an exceedingly small number of studies that have identified molecular changes in these pathologies. We aim to identify and compare DNA copy number alterations and gene expression changes between MF and LPP to highlight the similarities and the differences between these pathologies. Materials and Methods: The patients were prospectively selected from University Clinic of Dermatology and Venereology Timișoara, Romania. From fresh frozen skin biopsies, we extracted DNA using single nucleotide polymorphism (SNP) data. The use of SNP array for copy number profiling is a promising approach for genome-wide analysis. Results: After reviewing each group, we observed that the histograms generated for chromosome 1–22 were remarkably similar and had a lot of CNAs in common, but also significant differences were seen. Conclusions: This study took a step forward in finding out the differences and similarities between MF and LPP, for a more specific and implicitly correct approach of the case. The similarity between these two pathologies in terms of CNAs is striking, emphasizing once again the difficulty of approaching and differentiating them.

Identification of biparental and diploid blastocysts from monopronuclear zygotes with the use of a single-nucleotide polymorphism array

To select normal fertilized diploid blastocysts in patients who had only monopronucleated (1PN) embryos for transfer. Experimental study. University-affiliated center. Couples who were undergoing intracytoplasmic sperm injection treatment and had 1PN blastocysts. In a preliminary test, limited cells of parthenogenetic human embryonic stem cells (phESCs) and normal fertilized blastocysts were analyzed with the use of a low-density single-nucleotide polymorphism (SNP) array to identify the distribution pattern and rate of heterozygosity. In the clinical application, 1PN blastocysts were analyzed with the use of the SNP array. Only diagnosed normal blastocysts were transferred. The diagnosed uniparental blastocysts were validated by imprinted gene expression. Distribution pattern and rate of heterozygosity between parthenogenesis and normal fertilization. In the pretest, phESCs exhibited distinct distribution pattern and lower rate of heterozygosity, compared with normal fertilized blastocysts after SNP analysis. In particular, homozygous hESCs showed a panhomozygosity distribution pattern, hybrid phESCs showed a partial homozygosity distribution pattern, and normal fertilized blastocysts exhibited a panheterozygosity distribution pattern with an average of 20.21% heterozygosity rate; 13.6% was found to be the minimum cutoff to predict normal fertilized samples. In the clinical application, 24 1PN blastocysts were analyzed; 10/24 showed chromosomal abnormalities, 3/24 showed panhomozygosity with 0.45%-0.8% heterozygosity, and 1/24 showed partial homozygosity with 6.54% heterozygosity. The remaining 10 blastocysts, with a panheterozygosity distribution pattern and higher genomic heterozygosity rate, were diagnosed as normal-fertilization diploid embryos; three were transferred and resulted in two healthy newborns. The low-density SNP array might serve as a cost-effective method to identify biparental origin and diploid 1PN blastocysts for transfer.

Single-nucleotide polymorphism array (SNP-A) improves the identification of chromosomal abnormalities by metaphase cytogenetics in myelodysplastic syndrome

AimsThe myelodysplastic syndromes (MDS) are a heterogeneous group of clonal haematopoietic stem cell disorders characterised by inefficient haematopoiesis and risk of progression to acute myeloid leukaemia. Metaphase cytogenetics is an...

SNP arrays: comparing diagnostic yields for four platforms in children with developmental delay.

BackgroundMolecular karyotyping is now the first-tier genetic test for patients affected with unexplained intellectual disability (ID) and/or multiple congenital anomalies (MCA), since it identifies a pathogenic copy number variation (CNV) in 10-14% of them. High-resolution microarrays combining molecular karyotyping and single nucleotide polymorphism (SNP) genotyping were recently introduced to the market. In addition to identifying CNVs, these platforms detect loss of heterozygosity (LOH), which can indicate the presence of a homozygous mutation or uniparental disomy. Since these abnormalities can be associated with ID and/or MCA, their detection is of particular interest for patients whose phenotype remains unexplained. However, the diagnostic yield obtained with these platforms is not confirmed, and the real clinical value of LOH detection has not been established.MethodsWe selected 21 children affected with ID, with or without congenital malformations, for whom standard genetic analyses failed to provide a diagnosis. We performed high-resolution SNP array analysis with four platforms (Affymetrix Genome-Wide Human SNP Array 6.0, Affymetrix Cytogenetics Whole-Genome 2.7 M array, Illumina HumanOmni1-Quad BeadChip, and Illumina HumanCytoSNP-12 DNA Analysis BeadChip) on whole-blood samples obtained from children and their parents to detect pathogenic CNVs and LOHs, and compared the results with those obtained on a moderate resolution array-based comparative genomic hybridization platform (NimbleGen CGX-12 Cytogenetics Array), already used in the clinical setting.ResultsWe identified a total of four pathogenic CNVs in three patients, and all arrays successfully detected them. With the SNP arrays, we also identified a LOH containing a gene associated with a recessive disorder consistent with the patient’s phenotype (i.e., an informative LOH) in four children (including two siblings). A homozygous mutation within the informative LOH was found in three of these patients. Therefore, we were able to increase the diagnostic yield from 14.3% to 28.6% as a result of the information provided by LOHs.ConclusionsThis study shows the clinical usefulness of SNP arrays in children with ID, since they successfully detect pathogenic CNVs, identify informative LOHs that can lead to the diagnosis of a recessive disorder. It also highlights some challenges associated with the use of SNP arrays in a clinical laboratory.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-014-0070-0) contains supplementary material, which is available to authorized users.

Different Characteristics Identified by Single Nucleotide Polymorphism Array Analsysis in Leukemia Suggest the Need for Different Application Strategics Depending On Disease Category.

AbstractAbstract 2490 Background:High resolution SNP-A (single nucleotide polymorphism array) based karyotyping has become one of the most useful tools to investigate complex genomic lesions in leukemic cells. SNP-A has the potential to be applied as a diagnostic tool and as a surrogate for prognostic stratification in leukemias. As such, SNP-A should be a valuable asset in the diagnostic flow in clinical cytogenetic setting. However, due to limited laboratory and health care resources, its application needs to be decided carefully with a reasonable guideline. The present study investigated the value of SNP-A as an array based karyotyping tool in 469 cases with leukemias/MDS. The detection rate of SNP-A based karyotyping in combination with metaphase cytogenetics (MC) was assessed, with the goal of proposing a practical approach for clinical applications of SNP-A in leukemias/MDS. Material and Methods:Four hundred sixty nine patients with diverse subtypes of leukemia were included; 133 AML with normal karyotype (AML-NK), 98 AML with core binding factor rearrangement (CBF-AML), 61 MDS including chronic myelomonocytic leukemia, 118 CML in chronic phase (CML-CP), and 59 ALL (B-lineage). The Genome-Wide Human SNP 6.0 Array (Affymetrix, Santa Clara, CA, USA) was performed. Results:In the 469 patients, the detection rate was 20%(96/469) by MC alone, 33%(156/469) by SNP-A alone, and 39%(184/469) by combined use of SNP-A and MC. According to subtype of leukemias/MDS, the detection rate identified by SNP-A was different and the incidence of CN-LOH varied. In addition, each leukemia subtype showed a different pattern in terms of their types, sizes, and locations of copy number alterations and CN-LOH lesions.SNP-A detected chromosomal lesions not identified by MC, especially in AML-NK with a detection rate of 32%(43/133). In CBF-AML, the detection rates by MC alone and combined use of MC and SNP-A were 29%(28/98) and 40%(39/98), respectively. AML-NK showed more frequent CN-LOH (23%,31/133) than CBF-AML (3%,3/98). In AML-NK, loss of lesions occurred predominantly on 17p, 17q, or 7q. In AML-CBF, 8q or 9q was the common site of loss lesions. Trisomy 8 and CN-LOH of 13q were common lesions in both AML-NK and AML-CBF.As for MDS, t he detection was improved to 54%(33/61) by combined SNP-A and MC, compared with 39%(24/61) using MC alone. MDS showed frequent CN-LOH (25%,15/61) on 11q or 14q. Consistent with MC, loss lesions were frequently found on 5q, 7q, or 20q. In one patient with del(9q) as a sole abnormality, CN-LOH of 7q (26 Mb) was found by SNP-A.In ALL, detection was improved to 88%(51/59) by using combined SNP-A and MC, compared with 63%(37/59) by MC alone and CN-LOH was found in 20%(12/59) of patients. Concerning the size of abnormal lesions, the median size of loss in ALL was smaller than those of other leukemia subtypes. The size of focal deletions of IKZF 1, ETV 6, and CDKN 2A was 106–282 kb, 370 kb-4.5 Mb, and 115 kb-2.1 Mb, respectively. Furthermore, in ALL, aneuploidy abnormalities were accurately identified by SNP-A. ALL case with normal karyotype by MC showed gain or loss of several whole chromosomes by SNP-A, suggesting presence of hyperdiploidy clones or hypodiploidy clones. In particular, in a case showing chromosome numbers of 46–60 by MC, SNP-A revealed two kinds of abnormal lesions; CN-LOH and gain (tetrasomy) on several whole chromosomes, consistent with doubling of a near-haploid clone.In CML, t he detection rates of MC alone and combined use of MC and SNP-A was 3%(4/118) and 24%(28/118), respectively. Among abnormal lesions identified by SNP-A, 90% (35/39) were losses; 83%(29/35) were submicroscopic 9q34 or/and 22q11.2 deletions adjacent to the t(9;22) breakpoint. CN-LOH was found only in 2%(2/118) in CML-CP. Conclusion:The present study shows that SNP-A is useful to improve the detection rate of genomic lesions in diverse leukemia subtypes. The decision to perform SNP-A in addition to MC and/or FISH should be made according to the disease category of each leukemia subtype. In AML, it would be better that SNP-A is used depending on the karyotypic results by MC, while routine SNP-A appears to be an efficient screening method in MDS and ALL and the benefit is minimal in CML A consensus needs to be reached between laboratories as to the practical strategies for the clinical application of SNP-A. Disclosures:No relevant conflicts of interest to declare.

Total Genomic Loss Detected by High-Density Single Nucleotide Polymorphism Array Is Predictive of Azacitidine Response in Very Poor IPSS-Revised MDS or AML Patients

AbstractAbstract 4936 Background:Azacitidine (AZA) has changed the outcome of patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia with multi-lineage dysplasia (AML-MLD) unfit for intensive chemotherapy. AZA is a hypomethylating agent providing about 50% of responses in MDS and AML with low blast count (Fenaux et al., Lancet Oncol 2009, JCO 2010). IPSS-R scoring was evaluated in MDS and AML with 20–29% of blasts untreated patients. Conventional cytogenetic have major prognostic interest in this score (Schanz et al., JCO 2012). To date, SNP array analysis are not included in scoring system and no markers of AZA response have been identified with this analysis.Methods: This analysis included MDS and WHO-AML-MLD (>30% blasts) patients treated by AZA in 6 centers. Genomewide single nucleotide polymorphism (SNP) analysis using SNP 6. 0 arrays (Affymetrix, High Wycombe, U. K) was performed on bone marrow (BM) samples. Patients having received ≥ 1 cycle of AZA and who had bone marrow evaluation after ≥ 4 cycles, or who died or progressed before completion of 4 cycles were considered evaluable (the last 2 groups were considered as treatment failures). Responses were scored according to IWG 2006 criteria for MDS and to Cheson et al. (JCO 2003) for AML. DNAs were extracted for hybridization according to the manufacturers’ recommendations (Qiagen). Affymetrix CEL files for each sample were analyzed using the Genotyping Console software (v3. 0. 2). Genotyping was performed using Birdseed V2 algorithm. Unpaired Copy Number and LOH analysis was performed with Regional GC correction. For each patient, size of all deletions (loss) find with GC was added to have a total deletion size. The same was performed for total gain size.Results: The study population included 51 patients: F/M: 23/28; median age 73 (range 42–88). Diagnosis at AZA onset was RAEB-2 in 19 patients (IPSS int-1 in 4, int-2 in 10, high in 5) and WHO-AML-MLD in 32 patients. Cytogenetic according to IPSS-R was good in 23, intermediate in 9, poor in 7 and very poor in 12. IPSS-R score was good in 1 patient, intermediate in 4 patients, poor in 25 patients and very poor in 21 patients. Median number of cycles was 7 (range 1–42). All patients received the approved (75mg/m2 for 7 days every 4 weeks) or a reduced AZA schedule (75 mg/m2 for 5 days every 4 weeks). Median overall survival (OS) of our cohort was 11 months. DNA samples from all patients were available for SNP analysis. In using smoothing spline Cox model analysis, we observed that relative risk (RR) of worse OS increased above 4 megabases (Mb) of total chromosomal loss size detected with SNP array. Increase of RR was found in IPSS-R intermediate, poor and very poor. OS of patients treated by AZA with more than 4 Mb of genomic loss detected by SNP array was significantly different of OS of patients with less than 4 Mb (6 months vs 14 months respectively, p=0. 0012). Negative effect of genomic loss above 4 Mb was mainly observed in IPSS-R very poor group. In IPSS-R very poor subgroup, we observed significant difference in OS between patients with more than 4 Mb of genomic loss versus patients with less than 4Mb (3 months vs 10 months respectively, p=0. 01). In our cohort, total genomic gain has no impact on OS.Conclusion: New tools such as SNP array are not used in current practice. Therefore, prognostic impact of molecular karyotype is unclear in MDS/AML treated by AZA; our data suggest that total genomic loss superior to 4 Mb could be a worse prognosis, mainly in IPSS-R very poor patients. Impact of SNP array should be studied in larger cohort of patients treated by AZA in order to validate these results. Starczynowski et al. (Blood 2008) showed that total genomic alterations superior to 3Mb were associated with a poor OS in low-risk MDS. Taken together, these data are in favor of the use of SNP array's parameters in future prognosis scoring system. Disclosures:No relevant conflicts of interest to declare.

Different characteristics identified by single nucleotide polymorphism array analysis in leukemia suggest the need for different application strategies depending on disease category

The purpose of this study was to evaluate the detection rate of chromosomal rearrangements in leukemia using single nucleotide polymorphism array (SNP-A) in combination with metaphase cytogenetics (MC), with the aim of proposing a practical approach for clinical karyotyping applications of SNP-A. The Genome-Wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA) was applied in 469 patients with a variety of hematologic malignancies. Combined use of SNP-A with MC improved the detection rate in comparison with MC alone: acute myeloid leukemia (AML) with normal karyotype (NK), 32% versus 0%; core binding factor (CBF)-AML 40% versus 29%; myelodysplastic syndrome (MDS), 54% versus 39%; chronic myeloid leukemia (CML), 24% versus 3%; and acute lymphoblastic leukemia (ALL), 88% versus 63%. Different patterns of abnormalities (especially the type, size, and location) were noted in the leukemia subtypes. Copy neutral loss of heterozygosity lesions was detected in 23% of AML-NK, 3% of CBF-AML, 25% of MDS, 2% of CML, and 20% of ALL. SNP-A also provided information on cryptic deletions and a variety of aneuploidies in ALL, while the benefit was minimal in CML. In conclusion, different patterns of abnormal lesions were presented according to the disease category, thus requiring a different approach of adopting SNP-A-based karyotyping among different leukemia subtypes.

A genome‐wide single‐nucleotide polymorphism‐array can improve the prognostic stratification of the core binding factor acute myeloid leukemia

Core binding factor (CBF) AML with the D816 C-KIT gene mutation demonstrate inferior treatment outcomes. However, the remaining cases without the D816 C-KIT mutation imply a requirement of more sophisticated dissection of the patients according to their prognosis. In this study, we analyzed the prognostic value of a single nucleotide polymorphism array (SNP-A) based karyotyping combined with metaphase cytogenetics (MC) to facilitate further stratification of CBF AML patients. A total of 98 CBF AML patients were included and genome-wide Human SNP 6.0 Arrays (Affymetrix) were performed using marrow samples taken at diagnosis. Overall, 40 abnormal lesions were identified in 25 patients (26%). Survival of the patients with the abnormal lesion(s) detected by SNP-A and/or MC was worse than those without lesions in terms of the 2-year overall survival (OS; 57.5% vs. 76.4%, P = 0.028), event-free (EFS; 45.7% vs. 66.2%, P = 0.072), and leukemia-free survival (LFS; 49.0% vs. 77.4%, P = 0.015), specially in the subgroup with inv(16)/t(16;16) (40.9% vs. 80.2% OS, P = 0.040) and in the subgroup without the D816 C-KIT mutation (61.6% vs. 82.7% OS, P = 0.038). Multivariate analysis confirmed the prognostic impact of the abnormal SNP-A and/or MC lesion on EFS (HR 2.011, P = 0.047), and LFS (HR 3.231, P = 0.005) in the overall CBF AML. This study suggests that the combined use of SNP-A with MC in the CBF AML can provide important prognostic value, especially in the inv(16)/t(16;16) subgroup or in the patients without the D816 C-KIT mutation.

Genome-Wide Single-Nucleotide Polymorphism-Array Can Improve Prognostic Stratification of Core Binding Factor Acute Myeloid Leukemia, Especially in the Subgroup with Inv(16)/t(16;16) or without D816 C-KIT Mutation,

Abstract 3515 Background:The core binding factor (CBF) AML can be achieved long-term remission with high dose cytarabine-based chemotherapy alone. However, those with C-KIT gene mutation (esp. D816 C-KIT mutation) showed worse treatment outcomes compared to those with wild type C-KIT gene. The remaining cases without D816 C-KIT mutation is around 75% of CBF AML, which implies requirement of more sophisticated dissection of the patients according to their prognosis. Single nucleotide polymorphism (SNP) array (SNP-A) could detect cryptic abnormal genomic lesions, not identified by metaphase cytogenetics(MC). In this study, we analyzed the prognostic value of SNP-A based karyotyping combined with MC and its association with C-KIT mutation to facilitate further stratification of CBF AML patients. Methods and Materials:A total of 98 CBF AML patients were included and of whom, 63 (64%) and 35 patients (36%) were t(8;21) and inv(16)/t(16;16), respectively. Genome-Wide Human SNP 6.0 Array (Affymetrix, CA, USA) was performed using DNAs from marrow samples taken at diagnosis. Results:A total of 40 abnormal genomic lesions in 25 patients (26%) were detected by SNP-A karyotyping analysis, with a mean of 1.6 lesions per affected case (median size 33.6 Mb; range 0.4–145.9 Mb), including 3 CN-LOH lesions, 17 gain lesions, and 20 loss lesions. Survival of the patients with abnormal lesion(s) detected by SNP-A or/and MC was worse than those without any lesions in terms of 2 years’ overall survival (OS; 57.5% vs 76.4%, p=0.028), event-free (EFS; 45.7% vs 66.2%, p=0.072) and leukemia free survival (LFS; 49.0% vs 77.4%, p=0.015). In contrast, MC alone could not stratify patients according to their long-term prognosis. Especially, in the subgroup with inv(16)/t(16;16), survival of patients with abnormal SNP-A/MC lesion showed worse than that of those without lesion (40.9±12.7% vs 80.2±10.4% at 2 yrs, p=0.040), but not in the subgroup with t(8;21) (66.85±9.1% vs 74.4±7.8% at 2 yrs, p=0.240). As for the subgroup with D816 C-KIT mutation, there were no differences of OS (p=0.417), EFS (p=0.380) and LFS (p=0.218) according to the presence of abnormal lesions detected by either SNP-A or MC. However, in the subgroup without D816 C-KIT mutation, those with abnormal lesions detected by either SNP-A or MC showed worse survival compared to those without abnormal lesions with respect to OS (61.6±8.7% vs 82.7±5.6% at 2 yrs, p=0.038). Multivariate analysis confirmed prognostic impact of abnormal SNP/MC lesions on OS (HR 2.743, p=0.020), EFS (HR 2.434, p=0.025), and LFS (HR 3.350, p=0.012). Conclusion:This study suggests that combined use of SNP-A with MC in the initial evaluation of CBF AML can provide an important prognostic value, especially in the inv(16)/t(16;16) subgroup or in the patients without having D816 C-KIT mutation. Disclosures:No relevant conflicts of interest to declare.

Abstract 1781: Use of SNP arrays to assess loss of heterozygosity in gliomas

Abstract Introduction: Loss of heterozygosity (LOH) of chromosome arms 1p and 19q in gliomas has diagnostic, prognostic, and therapeutic implications. The deletion of 1p and the codeletion of chromosome arms 1p and 19q correlate with the diagnosis of oligodendroglioma, increased chemosensitivity and improved prognosis. Clinically, LOH is most frequently determined by Fluorescent In Situ Hybridization (FISH) and short tandem repeat (STR) analysis. Each approach suffers from the limitation that the probes/primers interrogate only a small portion of the chromosomes. Small deletions can be misinterpreted as LOH of the entire chromosome arm. We have investigated the use of a single nucleotide polymorphism (SNP) array for identifying LOH in gliomas. Methods: Genomic DNA was extracted from 5 formalin-fixed paraffin-embedded tissue samples following microdissection, and from peripheral blood. Samples were run on an ABI 3100 following multiplex PCR amplification of 5 STRs on chromosome 1p (D1S199, D1S186, D1S162, D1S312, D1S226) and 3 STRs on chromosome 19q (D19S918, D19S112, D19S206). Array analysis was performed using the Affymetrix genome-wide human SNP array 6.0 platform (906,600 SNPs) according to protocol. Data were analyzed with Partek Genomics Suite. Results: Cases 1 and 4 showed no LOH on chromosomes 1p and 19q by STR analysis and SNP array. Cases 2 and 5 showed LOH on chromosomes 1p and 19q by STR analysis and SNP array. Case 3 showed partial centromeric LOH on chromosome 1p by STR analysis which was confirmed by SNP array. Case 1 was a 48 year old male with anaplastic mixed oligoastrocytoma. Additional SNP array findings included a deletion of chromosome arm 13q. Case 4 was a 31 year old female with a low grade glioneural tumor, and no additional findings were made by SNP array. Case 2 was a 47 year old female with anaplastic oligodendroglioma. Additional SNP array findings included losses on chromosomes 5, 6, 9,15, and whole gain of chromosome 11. Case 5 was a 12 year old male with anaplastic oligodendroglioma. SNP array found additional losses on chromosomes 2, 3, 6, 8, 9, 10, and 20. Case 3 was a 47 year old female with an astrocytoma. Analysis of the 3 most centromeric STR loci on 1p demonstrated allelic imbalance that was consistent with LOH. The 2 most telomeric STR loci demonstrated allele ratios consistent with heterozygosity (negative for LOH). SNP array confirmed partial centromeric LOH on 1p and identified losses on chromosomes 2, 6, 10, 13, 16, and 22. Conclusion: Analysis of LOH on chromosome arms 1p and 19q by STR analysis and SNP array were concordant. SNP array identified additional gains or losses in each sample that were not detected by the STR assay. Interestingly, SNP array analysis also identified LOH on chromosome 13q, which contains the BRCA2 gene locus, in cases 1 and 3. If a second-hit can be identified, this may present a novel approach for identifying glioma patients who may potentially benefit from Poly (ADP-Ribose) Polymerase (PARP) inhibitor therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1781.