879P Whole-genome landscape of head and neck melanomas in East Asia (China)

Abstract

Head and neck melanomas are a heterogeneous group of tumors that may arise from abnormal melanocytes in various sites, such as scalp of the head, conjunctiva, nasal pharyngeal and oral cavity.Despite their close anatomical location, melanomas from different sites of the head and neck have widely different histological structures, biological behaviors, genetic characteristics, and prognosis. However, researches on genomic landscape of head and neck melanoma in East Asian patients are still sparse. We performed whole-genome sequencing (WES) and clinical profiling on 40 head and neck melanoma samples, including 8 conjunctival melanoma of the eyes, 7 scalp of the head, 10 nasal and 15 oral cavity. All the samples were derived from East Asian populations. We show that tumors from eyes and head tended to harbor more substitution/indel (SNVs) than those from nasal and oral. Percent of the genome affected by copy number variants was no significant differences among the four sites. Head and neck melanomas samples had more genetic aberations in genes within the RTK-RAS pathway and NOTCH pathway. BRAF, NRAS were identified as significantly mutated genes (SMGs).Eyes and head tumors had consistent mutational signature, while the oral and nasal tumors had similar mutationnal signature. The number and type of structural rearrangements varied dramatically among the four sites, suggesting the implication of distinctive mutational processes. Somatic arm level CNV alterations including amplification at chromosomes 1q, 6p, 7 and deletions at chromosomes 6q, 10, 13q, 16q, 18p, 19.Significantly amplified regions, included those containing 1q22(MUC1), 3p13(MITF), 4q12(KIT), 5p15.33 (TERT), 6p23, 7p22.1(RAC1), 8q24.3(MYC), 9q34.3(NOTCH1),11q14.1(PAK1,GAB2), 12q14.1(CDK4), 17q25.1, 20q13.2. as well as deleted regions 3q22.2, 6q26, 9p21.3-24.3(CDKN2A,CDKN2B), 10q26.13, 11q23.3, 16p12.1, 11q22.3(ATM). Here, we provided a detailed view of the genomic landscape of East Asian head and neck melanomas at different sites, which might extend our current understanding of head and neck melanoma.