Abstract 647: Identification of novel and known hotspot variants in African Americans with colorectal cancer

Abstract

Abstract Background: The recent introduction of the cancer hotspot panel can help enhance targeted cancer therapy, but requires further refinement to identify which genes have significant clinical value for the population of interest. We aim to determine such genes by identifying somatic alterations in the 48 cancer gene panel in African Americans. Methods: Tumor matched normal tissues (n=16) from African American colorectal cancer patients were analyzed using a 48 hotspot cancer panel by Ion Torrent sequencing. Variants of the genes found in TruSeq Amplicon - Cancer Panel (TSACP) were identified and validated. The type of variant was determined using bioinformatic pipelines including Ensembl's Variant Effect Predictor. The genes with relevant clinical value were determined based on frequency of somatic variants and results from previous studies. Results: Somatic variants were detected in 39/48 (82%) genes. Of the 39 genes, the 7 with the most clinical value were selected for further analysis. Overall, 46 novel and known hotspot somatic variants were determined in the following 7 genes: KRAS (7/46 [15%]), NRAS (2/46 [4%]), MLH1 (1/46 [2%]), PIK3CA (8/46 [18%]), SMAD4 (6/46 [13%]), RET (9/46 [20%]), and TP53 (13/46 [28%]). Of the KRAS variants, 57% (4/7) were found in codons 12 and 13 while the other 43% (3/7) were found in codons 117 and 146. Out of the 46 somatic variants, 30% (14/46) were in hotspot regions. Of the KRAS hotspot variants, 100% (4/4) were in codons 12 and 13. The 2 NRAS variants were in codons 59 and 61. Lastly, the 9 genes without variants in our population are CDKN2A, SMARCB1, AKT1, ALK, FGFR2, IDH2, CSF1R, HNF1A and MPL. Conclusion: We have identified novel and known hotspot somatic variants in African Americans with colorectal lesions. Patients with significant hotspot variants, primarily missense alterations, had a worse prognosis. As a result, cancer gene panel hotspot profile should be taken into consideration when treating African American CRC patients. Citation Format: Hassan Brim, Payaam Tavakoli, Mohammad Reza Daremipouran, Babak Shokrani, Edward Lee, Mehdi Nouraie, Adeinko O. Laiyemo, Hassan Ashktorab. Identification of novel and known hotspot variants in African Americans with colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 647.