Methylthioadenosine phosphorylase inactivation depends on gene deletion in laryngeal squamous cell carcinoma

Histopathology. 2012 Dec;61(6):1082-8. doi: 10.1111/j.1365-2559.2012.04353.x. Epub 2012 Sep 28.

Abstract

Aims: Methylthioadenosine phosphorylase (MTAP) is an essential enzyme for the methionine and adenosine salvage pathway in normal cells, frequently inactivated in many different human cancers. MTAP status could be important for tumour cell sensitivity to adjuvant chemotherapy. To our knowledge, there have been no reports to date on MTAP status in laryngeal carcinoma.

Methods and results: A series of 31 laryngeal squamous cell carcinomas was investigated for MTAP mRNA expression using reverse transcription and quantitative polymerase chain reaction (qPCR), as well as for MTAP gene deletion and/or promoter hypermethylation using qPCR and methylation-specific PCR, respectively. Low MTAP mRNA expression was found in 32% of cases, and was associated with MTAP gene deletion (in 70%; P<0.001) but not with MTAP promoter hypermethylation, indicating that, in this tumour, gene deletion is the main mechanism for MTAP inactivation. Neither low mRNA expression nor gene deletion was associated with any of the clinicopathological parameters investigated.

Conclusion: Given the significance of MTAP status for cell sensitivity to different chemotherapeutic regimens, our results suggest that determination of MTAP inactivation should be taken into consideration in managing laryngeal squamous cell carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Disease Management
  • Follow-Up Studies
  • Gene Deletion*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Laryngeal Neoplasms / drug therapy
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / metabolism
  • Male
  • Middle Aged
  • Purine-Nucleoside Phosphorylase / genetics*
  • Purine-Nucleoside Phosphorylase / metabolism
  • RNA, Messenger / metabolism
  • Treatment Outcome

Substances

  • RNA, Messenger
  • Purine-Nucleoside Phosphorylase
  • 5'-methylthioadenosine phosphorylase