A selected group of large common fragile site genes have decreased expression in oropharyngeal squamous cell carcinomas

Ge Gao, Jan L. Kasperbauer, Nicole M. Tombers, Vivian Wang, Kevin Mayer, David I. Smith

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The common fragile sites (CFSs) are large regions of profound genomic instability found in all individuals. The frequent deletions and other alterations in these regions in multiple cancers has led to the discovery of a number of extremely large genes contained within these regions and several of the large CFS genes have already been demonstrated to function as tumor suppressors involved in the formation of many different cancers. To study the large CFS genes in oropharyngeal squamous cell carcinoma (OPSCC), we did RNA seq analysis from 11 head and neck cancer patients. This revealed that there are six large CFS genes which consistently had decreased expression in the tumor samples compared to their matched normal tissues. These six genes are PARK2, DLG2, NBEA, CTNNA3, DMD, and FHIT. PARK2 and FHIT are located within the two most frequently expressed CFSs and both have been demonstrated to function as tumor suppressors, while the other large genes are found to have frequent alterations in multiple cancers. Validation experiments using real time PCR indicated that over 60% of OPSCC tumors showed decreased expression for all six genes. Both HPV-positive and HPV-negative OPSCCs had similar proportions with loss of expression of these genes. Our results suggest that this selected group of large genes might serve as potential tumor suppressors involved in the development of OPSCCs. Further studies are needed to investigate whether the decreased expression observed is due to genomic instability within the CFS regions or the selection for alterations of specific large CFS genes.

Original languageEnglish (US)
Pages (from-to)392-401
Number of pages10
JournalGenes Chromosomes and Cancer
Volume53
Issue number5
DOIs
StatePublished - May 2014

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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