Detection of new PTEN/MMAC1 mutations in head and neck squamous cell carcinomas with loss of chromosome 10

Alterations of the candidate tumor suppressor gene PTEN/MMAC1 and the cell cycle control gene p16(CDKN2/MTS-1/INK4a) have been detected in many types of human cancer. Here, we wanted to study the role of PTEN/MMAC1 in head and neck squamous cell carcinomas (HNSCC) in correlation to mutation and methylation of p16 and to previous in situ hybridization results concerning loss of chromosomes 9 and 10. We screened for alterations of PTEN/MMAC1 and p16 in 52 HNSCC of different sites. Mutations of PTEN/MMAC1 were found in 23% of tumor samples (missense mutations in 7 carcinomas, 13%). A loss of chromosome 10 was detected in five carcinomas with missense PTEN/MMAC1 mutations (71%). The missense mutations of PTEN/MMAC1 occurred in exons 5 (five different mutations in the neighborhood of the protein tyrosine phosphatase domain), 6, 7, and 8. Only one of these mutations had been described before. In addition, in three laryngeal carcinomas (6%), missense mutations of p16 (in exon 2) were detected and 14% of carcinomas showed a methylation of p16. Our results focus on the essential but not solitary role of PTEN/MMAC1 in the tumorigenesis or progression of a subset of HNSCC.