Genomic and Transcriptomic Characterization Links Cell Lines with Aggressive Head and Neck Cancers

Hui Cheng,Xinping Yang,Han Si,Anthony D Saleh,Wenming Xiao,Jamie Coupar,Susanne M Gollin,Robert L Ferris,Natalia Issaeva,Wendell G Yarbrough,Mark E Prince,Thomas E Carey,Carter Van Waes,Zhong Chen

doi:10.1016/j.celrep.2018.10.007

Abstract

SUMMARYCell lines are important tools for biological and preclinical investigation, and establishing their relationship to genomic alterations in tumors could accelerate functional and therapeutic discoveries. We conducted integrated analyses of genomic and transcriptomic profiles of 15 human papillomavirus (HPV)-negative and 11 HPV-positive head and neck squamous cell carcinoma (HNSCC) lines to compare with 279 tumors from The Cancer Genome Atlas (TCGA). We identified recurrent amplifications on chromosomes 3q22–29, 5p15, 11q13/22, and 8p11 that drive increased expression of more than 100 genes in cell lines and tumors. These alterations, together with loss or mutations of tumor suppressor genes, converge on important signaling pathways, recapitulating the genomic landscape of aggressive HNSCCs. Among these, concurrent 3q26.3 amplification and TP53 mutation in most HPV(–) cell lines reflect tumors with worse survival. Our findings elucidate and validate genomic alterations underpinning numerous discoveries made with HNSCC lines and provide valuable models for future studies.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer by incidence worldwide (Torre et al, 2015)
Various chemical carcinogens, human papillomavirus (HPV) infection, and genetic predisposition contribute to the etiology of HNSCC and to the complex genetic alterations in tumor subsets that differ in prognosis and response to therapies (Van Waes and Musbahi, 2017)
DNA copy number alterations (CNAs) Identified in Cell Lines Recapitulate Those Found in Clinically Aggressive HNSCC Subsets in The Cancer Genome Atlas (TCGA) The panel of 15 HPV(À) and 11 HPV(+) HNSCC cell lines included 18 widely studied and genotype-verified lines (Brenner et al, 2010; White et al, 2007), and 8 recently derived lines, which are those with matched blood controls (Table S1A, indicated in the table as blood: Y)

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer by incidence worldwide (Torre et al, 2015). Establishing the functional role of genomic alterations in pathogenesis and as potential targets for therapy could be accelerated by genomic and transcriptomic characterization of a large panel of established cell line models differing in etiologic status. The extent to which HNSCC cell lines reflect the genomic and transcriptional alterations found in tumors remains unclear. Human cancer cell lines have long fostered mechanistic, genetic, molecular, cellular, and pharmacologic studies that were not possible using tumor specimens alone. Until the recent advent of massively parallel sequencing, it has not been possible to comprehensively determine if and how well historic and newer cell line panels with germline controls model genomic and transcriptomic alterations in tumor subtypes that differ in etiology, origin, and prognosis

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