New EPCAM founder deletion in Polish population

Area of Science:

• Genetics
• Oncology
• Molecular Diagnostics

Background:

• Founder mutations play a crucial role in hereditary cancer syndromes, impacting molecular diagnostics.
• Lynch syndrome (LS) is an inherited disorder increasing cancer risk, particularly colorectal cancer.
• The EPCAM gene is implicated in the etiology of LS.

Purpose of the Study:

• To report the identification and characterization of a founder mutation in the EPCAM gene.
• To investigate the prevalence and clinical significance of this EPCAM founder mutation in Polish families with Lynch syndrome.
• To assess the spectrum of cancers associated with this specific EPCAM mutation.

Main Methods:

• Genetic analysis of 8 Polish families.
• Mutation screening in the EPCAM gene, specifically the c.858+2478_*4507del deletion.
• Review of family cancer histories.

Main Results:

• A large deletion mutation (c.858+2478_*4507del) in the EPCAM gene was identified as a founder mutation.
• This mutation was present in 8 Polish families and is a common cause of LS in Poland.
• Colorectal cancer was the predominant malignancy, with occasional cases of pancreatic and gastric cancers observed.

Conclusions:

• The EPCAM founder mutation is a significant genetic factor contributing to Lynch syndrome in the Polish population.
• This finding highlights the importance of EPCAM mutation screening for LS diagnosis in this demographic.
• Understanding founder mutations like this one improves genetic counseling and cancer risk assessment.