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. 2021 Sep 23;6(1):78.
doi: 10.1038/s41525-021-00242-4.

MCM9 is associated with germline predisposition to early-onset cancer-clinical evidence

Yael Goldberg  1   2 , Ola Aleme  3 , Lilach Peled-Perets  3 , Sergi Castellvi-Bel  4 , Maartje Nielsen  5 , Stavit A Shalev  3   6
Affiliations

MCM9 is associated with germline predisposition to early-onset cancer-clinical evidence

Yael Goldberg et al. NPJ Genom Med. .

Abstract

Mutated MCM9 has been associated with primary ovarian insufficiency. Although MCM9 plays a role in genome maintenance and has been reported as a candidate gene in a few patients with inherited colorectal cancer (CRC), it has not been clearly established as a cancer predisposition gene. We re-evaluated family members with MCM9-associated fertility problems. The heterozygote parents had a few colonic polys. Three siblings had early-onset cancer: one had metastatic cervical cancer and two had early-onset CRC. Moreover, a review of the literature on MCM9 carriers revealed that of nine bi-allelic carriers reported, eight had early-onset cancer. We provide clinical evidence for MCM9 as a cancer germline predisposition gene associated with early-onset cancer and polyposis, mainly in a recessive inheritance pattern. These observations, coupled with the phenotype in knockout mice, suggest that diagnostic testing for polyposis, CRC, and infertility should include MCM9 analysis. Early screening protocols may be beneficial for carriers.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. MCM9 mutated pedigree.
Clinical manifestations, polyps, and cancers are indicated. Genotypes are indicated as: + for homozygotes; * for heterozygotes. Tumor spectrum included cancer—not otherwise specified, cervical cancer, colon polyps, colorectal cancer, medulloblastoma, oligo-terato-asthenozoospermia (OTA), and primary ovarian insufficiency (POI).
See this image and copyright information in PMC

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