A selected group of large common fragile site genes have decreased expression in oropharyngeal squamous cell carcinomas.
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.
Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Ge
G
Gao
Jan L
JL
Kasperbauer
Nicole M
NM
Tombers
Vivian
V
Wang
Kevin
K
Mayer
David I
DI
Smith
D017766:Acid Anhydride Hydrolases / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D043283:Chromosome Fragile Sites / Q000235:genetics*; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism; D005260:Female; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009960:Oropharynx / Q000378:metabolism* / Q000473:pathology; D027383:Papillomaviridae / Q000302:isolation & purification; D010610:Pharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D017423:Sequence Analysis, RNA; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D002352:Carrier Proteins; D016189:Dystrophin; D051528:Guanylate Kinases; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051178:alpha Catenin; D000099170:Bis(5'-adenosyl)triphosphatase; C441963:CTNNA3 protein, human; C484258:DMD protein, human; C498595:NBEA protein, human; C111567:parkin protein; C496468:DLG2 protein, human