The Winqvist group identifies a novel cancer susceptibility gene

Mutation in MCPH1 increases the risk of breast cancer threefold

A recent study by Professor Robert Winqvist´s group identifies a novel breast cancer predisposing mutation in the MCPH1 gene. This mutation was significantly more frequent among familial breast cancer cases (3,4%) than in the geographically matched healthy controls (0,4%).

The same mutation was also present in 1,4% (16/1150) of breast cancer cases not selected for or against family history of cancer or age at disease onset, and many of these cases turned out to have a family history of cancer as well. Besides breast cancer, one-third of the families with MCPH1 mutation exhibited also brain tumors and/or sarcomas.

Further studies showed that heterozygous MCPH1 mutation carriers exhibited a significant increase in genomic instability, and that the breast tumors of the mutation carriers had often lost the normal functional copy of MCPH1. These findings collectively establish MCPH1 as a novel breast cancer susceptibility gene.

The identified MCPH1 defect turned out to be a Finnish founder mutation, and based on its prevalence in the analyzed cohorts mutation carriers have at least moderate (3-fold), but potentially even high (up to eight-fold) risk for developing breast cancer.

The research, led by Adjunct Professor Katri Pylkäs and Professor Robert Winqvist at the University of Oulu, Finland, took advantage of recent technical and methodological advances by performing a massive parallel sequencing of hundreds of DNA damage response genes in Northern Finnish breast cancer cases with indication of hereditary disease susceptibility. The new mutation was discovered by PhD student Tuomo Mantere.

This research was published in PLOS Genetics, January 28th 2016, doi: 10.1371/journal.pgen.1005816

Mantere T, Winqvist R, Kauppila S, Grip M, Jukkola-Vuorinen A, Tervasmäki A, Rapakko K, Pylkäs K. Targeted Next-Generation Sequencing Identifies a Recurrent Mutation in MCPH1 Associating with Hereditary Breast Cancer Susceptibility.

Last updated: 2.9.2016