The ATM/p53 pathway is commonly targeted for inactivation in squamous cell carcinoma of the head and neck (SCCHN) by multiple molecular mechanisms.
The ATM/p53 pathway plays a critical role in maintenance of genome integrity and can be targeted for inactivation by a number of characterized mechanisms including somatic genetic/epigenetic alterations and expression of oncogenic viral proteins. Here, we examine a panel of 24 SCCHN tumors using various molecular approaches for the presence of human papillomavirus (HPV), mutations in the p53 gene and methylation of the ATM promoter. We observed that 30% of our SCCHN samples displayed the presence of HPV and all but one was HPV type 16. All HPV E6 gene-positive tumors exhibited E6 transcript expression. We observed 21% of the tumors harbored p53 mutations and 42% of tumors displayed ATM promoter methylation. The majority of tumors (71%) were positive for at least one of these events. These findings indicate that molecular events resulting in inactivation of the ATM/p53 pathway are common in SCCHN and can arise by a number of distinct mechanisms.
Bolt
Jennifer
J
Stanley S. Scott Cancer Center, LSU Health Sciences Center, New Orleans, LA, USA.
Vo
Quynh N
QN
Kim
Wan-Ju
WJ
McWhorter
Andrew J
AJ
Thomson
Jessica
J
Hagensee
Michael E
ME
Friedlander
Paul
P
Brown
Kevin D
KD
Gilbert
Jill
J
D064007:Ataxia Telangiectasia Mutated Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000821:virology; D018797:Cell Cycle Proteins / Q000235:genetics*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000821:virology; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases