Abstract 5347: Somatic mutation and overexpression of anaplastic lymphoma kinase (ALK) are uncommon events in Asian head and neck cancers

Abstract

Abstract Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that is frequently translocated in anaplastic large cell lymphoma (ALCL) and non-small cell lung cancer (NSCLC), etc. Gain-of-function mutations, largely mutations associated with resistance to ALK inhibitors, have been identified in neuroblastoma, colon adenocarcinoma and prostate adenocarcinoma, etc. Pan-cancer analysis of whole-exome sequencing data of >25 cancer types showed a mutational rate ranging from 0-9.4% across pan-cancers (www.cbioportal.org). In cancers of the head and neck, the potential role of ALK on precision treatment has been demonstrated in an Asian head and neck sarcomatoid carcinoma patient bearing an ALK aberration (Kim et al., 2015). In this study, we sought to examine the mutational rates of ALK in the US-TCGA HNSCC Provisional cohort, in a small Asian HNSCC cohort, as well as in Nasopharyngeal carcinoma (NPC, an Asian-prevalent HNC). Analysis of the whole-exome sequencing (WES) data of the US-TCGA HNSCC Provisional cohort (N=527; largely Caucasian ethnicity, 85.6%; www.cbioportal.org) revealed a somatic mutation rate of 4.0% (21 out of 527 patients, with 18 non-synonymous and 3 synonymous mutations) and a gene amplification rate of 0.4% (2 out of 522 tumors with copy number change data available). In contrast, the Asian prevalent Epstein-Barr Virus-associated NPC (N=102 micro-dissected tumors with paired blood samples analyzed by WES), no somatic ALK mutation was identified. Using a small Asian HNSCC cohort (N=16), next-generation sequencing (NGS) analysis with an ALK exon coverage of ~90% revealed no somatic ALK mutation, but the presence of Asian-predilected SNPs with unknown clinical or biological significance. Lastly, ALK protein expression, analyzed by Western blotting, was found to be low or largely undetectable in 25 Asian HNSCC tumors analyzed thus far. Yet, we cannot exclude the possibility of focal ALK expression in HNSCC tumors, which can be largely obscured by Western blotting. In conclusion, somatic mutation of ALK appears to be rare events in Asian HNSCC and EBV-associated Nasopharyngeal carcinoma. Acknowledgements: VWYL receives funding supports from the Research Grant Council, Hong Kong (General Research Fund: #1711484, #17121616; Theme-based Research: T12-401/13-R) and the Hong Kong Cancer Fund, Hong Kong. KWL receives funding from the Research Grant Council (Theme-based Research: T12-401/13-R), Hong Kong. WP is supported by Faculty Postdoctoral Fellowship Scheme from the Faculty of Medicine, Chinese University of Hong Kong. JYKC receives funding support by the Dr Stanley Ho Medical Foundation. Reference Kim, S. M., Kim, M. J., Jung, H. A., Sun, J. M., Choi, Y. L., Ko, Y. H., . . . Ahn, M. J. (2015) Presence of anaplastic lymphoma kinase translocation in sarcomatoid carcinoma of head and neck and treatment effect of crizotinib: A case series. Head Neck, 37(5), E66-69 Citation Format: Wenying Piao, Peony Hiu Yan Poon, Lan Wang, Chin Wang Lau, Jason Ying Kuen Chan, Yuxiong Su, Amy Bik Wan Chan, Hoi Lam Ngan, Kwok Wai Lo, Vivian Wai Yan Lui. Somatic mutation and overexpression of anaplastic lymphoma kinase (ALK) are uncommon events in Asian head and neck cancers [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 5347.