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9576 Background: The incidence of melanoma subtypes differs significantly among ethnicities. Ultraviolet (UV) radiation-driven melanomas are common in Caucasians, while non-cutaneous melanomas including acral and mucosal melanomas are more frequent in Asians. It will be of great interest and clinical relevance to decipher the molecular pathogenesis of different melanoma subtypes. Methods: We retrospectively studied a cohort of 89 Chinese melanoma patients who underwent surgical resection of their primary tumors followed by chemotherapy. Genomic profiling of primary melanomas was performed using next generation sequencing by targeting 422 cancer-relevant genes. The Kaplan-Meier method and logrank test were used for survival analysis, and a cox model was used for multivariate survival analysis. Results: Acral melanomas (54/89, 60%) were the most common subtype of this cohort, while cutaneous and mucosal subtypes accounted for 25% and 15%, respectively. Mutation profiling revealed that BRAF was most frequently mutated in cutaneous melanomas, but aberrant BRAF, RAS, KIT, and NF1 were almost evenly represented in acral and mucosal melanomas; of note, mucosal melanomas had a propensity for concurrent driver mutations. Chromosomal alterations were detected across all subtypes, and chr7p amplification significantly correlated with poor prognosis while independently of melanoma subtypes. Furthermore, acral and mucosal melanomas demonstrated higher rates of focal copy number variations (CNVs) than cutaneous melanomas. The amplification of CDK4/CCND1 and NOTCH2 was observed predominantly in acral melanomas , and RAD51 loss was significantly enriched in mucosal melanomas correlating with poor survival. In addition, the tumor mutation burden (TMB) was significantly lower in acral or mucosal melanomas than in cutaneous melanomas. Conclusions: Our findings revealed distinct patterns of driver mutations and chromosomal alterations in acral and mucosal melanomas in contrast to cutaneous melanoma, and highlighted the association of chromosome 7p amplification and RAD51 deletion with unfavourable survival in melanoma patients treated with standard chemotherapy.

247 Background: The genetic profile of primary urothelial carcinoma (UC) has been well documented but no reports analyze specific chromosomal alterations in metastatic disease. We performed molecular inversion probe array (MIP) analysis to compare chromosomal gains or losses in metastatic and primary UC samples. Methods: 33 samples of metastatic UC and 30 primary samples were analyzed from 48 patients (pts), of which paired primary and metastatic tissue was available for 14 pts. DNA from all samples was subjected to molecular inversion probe array analysis to identify focal areas of copy number gain (CNG) or loss (CNL). We focused this analysis on 21 genes from signaling pathways known to be of interest in UC (Table). CNG or CNL was defined as a log2 copy number ratio ≥ 0.8 or ≤ -0.8. GISTIC 2.0 was used to identify significantly altered regions. Results: In the loci analyzed, there were significantly more alterations in metastases than primary samples (8.4% vs 4.3% p=0.002). In particular, there was a significantly higher frequency of E2F3CNG in metastases (27% vs 7% p=0.046). There was frequent discordance in alterations when comparing primary and metastatic tissue from the same patients: 7 of 14 pts harbored potentially oncogenic CNG/CNL in their metastases that were not present in the primary. Conclusions: More alterations in UC-relevant genes were identified in metastases compared with primary tumors, in keeping with the multistep model of cumulative genetic change in cancer progression. More frequent CNG of the E2F3 gene was noted and may represent a mechanism of UC progression. Frequent discordance in alterations between primaries and metastases may be of significant clinical relevance in the future when selecting patients for appropriate molecularly targeted therapy. [Table: see text]

10585 Background: Neuroendocrine tumors (NETs) comprise a heterogeneous group of neoplasms containing biologically active peptides and amines in their cytoplasm. Anaplastic lymphoma kinase (ALK) tr...

e18513 Background: The 3q27 and 18q21 translocations are major chromosomal alterations in B cell lymphoma. Bcl-6 on chromosome 3q27 encodes B-cell lymphoma (Bcl)-6 protein, which inhibits different...

10537 Background: The identification of oncogenic chromosomal alterations in anaplastic lymphoma kinase (ALK) in lung cancer and neuroblastoma has revealed ALK as a potential candidate for anticanc...

5000 Background: We used a genome wide approach to identify chromosomal and gene expression alterations that might explain the aggressive clinical behavior of PC in AA compared with CA patients. Methods: We frequency matched 20 AA with 20 CA patients for potential confounding factors (PSA, age, Gleason grade, pathologic stage). We utilized array-CGH (Spectral Genomics), to identify noteworthy genomic regions with significantly different chromosomal alterations between the 2 groups. RNA samples were available for 19 AA and 14 CA patients. Gene expressions were examined using Affymetrix HG-U133 Plus 2.0 arrays. Correlations were examined between the noteworthy altered chromosomal regions and gene expression. Results: Regions of chromosomal gain or loss in each sample were determined using the circular binary segmentation approach coupled with an outlier detection method to identify singleton markers exhibiting alterations. We identified 28 chromosomal regions that were significantly different between the 2 cohorts (Fisher’s exact test). 11 regions (3q28- 29, 3q25–26, 4p12–14, 4p13, 9q21, 10q11, 11q14, 12p13, 14q12, 16p11, 20p11–20q11) were more commonly altered in AA patients compared to CA patients (P No significant financial relationships to disclose.

9551 Background: It is widely accepted that chromosomal instability is one of the essential features of cancer cells and that significant intratumoral heterogeneity based on the genetic changes may...

1568 Background: Oligodendroglial tumors are chemosensitive diseases. The evaluation by fluorescence in situ hybridization has been used to assess 1p and 19q alterations that are considered the bes...