Abstract B23: Targeted exome sequencing for effectors involving the MAPK and PI3K pathways of cutaneous melanoma in the minority population: Identifying unique molecular signatures
Authors: Morita Shane Y. 
Published: October 2015

Abstract
Background: Melanoma is a global problem, as its incidence is rising faster than any other malignancy for both men and women. Since Caucasians are primarily affected by melanoma, most of the clinical effort and patient education is focused on this cohort. In minorities, melanoma is usually detected at a more advanced stage, distributed on sun-protected areas and associated with a worse survival. Previous studies have depicted the relevance of alterations in the MAPK and PI3K pathways; however, inclusion of a multi-ethnic population comprising of unique groups such as Native Hawaiians, Pacific Islanders, Filipinos, and other Asians has been limited.
Methods: IRB approval was obtained for this retrospective analysis. From 2008 to 2013, 10 Asian/Pacific Islander patients histologically confirmed to have invasive conventional (non-acral) cutaneous melanoma were evaluated at a tertiary institution. Data including age, gender, tumor location, Breslow thickness, ulceration, and mitoses per mm squared were compiled. Using a cloud based in silica primer design software target genes was chosen. Multiplex primers were generated. Coverage was assessed using the University of California, Santa Cruz (UCSC) and National Center for Biotechnology Information (NCBI) genome browsers to ensure that known pathogenic single nucleotide polymorphisms were captured from the latest dbSNP genome build. Targets included AKT, BRAF, C-KIT, MEK, MTOR, NRAS, and PI3K. This pre-designed multiplexed panel contains genes across families representing driver mutations in signaling pathways. Next generation sequencing was performed using the Ion Torrent Personal Genome Machine™.
Results: Our findings demonstrated a unique molecular distribution. Interestingly in our non-Caucasian cohort of conventional melanoma, PI3K mutations were found in 30% (normally 2-6% in Caucasians) of the biospecimens, which supports our hypothesis that ethnic minorities may have a distinct biological profile. Furthermore, 40% of this minority cohort had a c-KIT mutation which is atypical for non-acral melanoma; in addition 2 of these c-KIT mutations were novel and not classically associated with melanoma in Caucasians. What is also compelling is that 50% had simultaneous mutations, including 30% that had a concomitant PI3K mutation. Demographics of the multi-ethnic cohort included mean age of 57.5 years (range 19-80) and male gender (4/10; 40 %). Tumor location primarily involved the extremity (8/10; 80%); median Breslow thickness was 1.97 mm (range 0.77-16.0), and mean mitoses per mm squared was 5.2 (range 0-16).
Conclusion: This is compelling data that may be applied to patient selection in future trials utilizing targeted agents and assist with gleaning insight into the mechanism of melanoma genesis. Molecular profiling diverse cohorts may improve the identification of novel molecular signatures germane to melanoma biology and therapy.
Note: This abstract was not presented at the conference.
Citation Format: Shane Y. Morita. Targeted exome sequencing for effectors involving the MAPK and PI3K pathways of cutaneous melanoma in the minority population: Identifying unique molecular signatures. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B23.