FaCD Online Syndrome Fact Sheet

Last updated: 30 Jan 2013

Name: POLD1 & POLE associated Colorectal Adenomas and Cancer

Mode of Inheritance: AD

Genes

POLD1, mapped to 19q13.33
POLE, mapped to 12q24.33

Tumor features

colorectal adenomas
colorectal cancer
endometrial cancer

Tumor features (possible)

brain tumor
colorectal hyperplastic polyps

Comment

Palles et al[1] identified 2 highly penetrant POLD1 (p.Ser478Asn) and 1 POLE (p.Leu424Val) germline mutation in group of 13 highly selected families with early onset microsatellite stable colorectal cancer (CRC), multiple colorectal adenomas (zero up to dozens) and a positive family history of colorectal cancer which included normal onset of CRC as well. The variants were subsequently tested in a series of 3,805 individuals of European ancestry with CRC, enriched for a family history of colorectal tumors, multiple adenomas and early-onset disease: a dozen additional families were identified. The variants were not detected in a large control series.

POLD1 appears to be associated with endometrial cancer and possibly brain tumors as well.

References

[1] Palles, C et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nature Genetics 2012; 45:136-144.