MSH2 splice site mutation and endometrial cancer

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Hereditary nonpolyposis colorectal cancer (HNPCC) is an inherited cancer susceptibility syndrome.
• Germ line mutations in mismatch repair (MMR) genes are the cause of HNPCC.
• MMR gene mutation carriers have increased risks for colorectal and other cancers, notably endometrial cancer.

Observation:

• This study describes an HNPCC patient with early-onset endometrial cancer and a family history of endometrial tumors.
• The patient harbored a germ line MSH2 splice site mutation (IVS9_2A>G).
• This mutation led to abnormal mRNA processing, a premature stop signal, and a truncated MSH2 protein.

Findings:

• The identified MSH2 mutation resulted in loss of MSH2 protein expression.
• The mutation was associated with high microsatellite instability.
• PTEN inactivation was also observed in conjunction with the MSH2 mutation.

Implications:

• The findings suggest a potential involvement of germ line MSH2 abnormalities in endometrial tumor development.
• These observations support the need for endometrial cancer screening in women from HNPCC families.
• Further research may elucidate the direct relationship between MSH2 mutations and endometrial cancer susceptibility.