Massive parallel sequencing in a family with rectal cancer

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Previous studies identified a family with suspected autosomal dominant rectal and gastric cancer syndrome.
• No causative genetic variant was previously identified, prompting further investigation into a potentially isolated rectal cancer syndrome within this family.

Purpose of the Study:

• To identify genetic variants associated with inherited rectal cancer in a specific family.
• To investigate potential novel genetic factors contributing to rectal cancer predisposition.

Main Methods:

• Whole-exome sequencing and whole-genome sequencing were performed on seven family members (six obligate carriers).
• Data were analyzed to identify shared coding, splicing, and structural variants among affected individuals.

Main Results:

• Six novel missense variants in genes CENPB, ZBTB20, CLINK, LRRC26, TRPM1, and NPEPL1 were identified.
• None of these genes have been previously associated with inherited rectal cancer.
• No structural variants were found.

Conclusions:

• Massive parallel sequencing revealed six potential genetic variants linked to rectal cancer in the studied family.
• The p.(Glu438Lys) variant in the CENPB gene warrants further investigation due to its role in DNA binding, centromere formation, and WNT signaling pathway involvement.
• These variants may represent high-risk or low-risk factors for inherited rectal cancer.