Deciphering inherited breast cancer susceptibility - Integrating diagnostic and novel genomic approaches

The focus of our Breast Cancer Genetics team is on resolving the molecular genetics and biology behind the inherited breast cancer predisposition.

Project information

Project duration


Project funder

Biocenter Oulu

Project coordinator

University of Oulu

Contact information

Project leader

Project description

The focus of our Breast Cancer Genetics team is on resolving the molecular genetics and biology behind the inherited breast cancer predisposition. For this we use breast cancer case cohorts collected from Northern Finnish population with homogenous genetic background and implement several high-throughput genomic methods for their comprehensive genetic analysis. The effects of the breast cancer predisposing variants are investigated with functional genomics, biochemical and tumor modelling approaches, which can provide important insights into the tumorigenesis mechanisms and may lead to implementation of more effective diagnostic and prognostic tools, as well as targeted treatment.

Key publications

Kumpula TA, Vorimo S, Mattila TT, O’Gorman L, Astuti G, Tervasmäki A, Koivuluoma S, Mattila TM, Grip M, Winqvist R, Kuismin O, Moilanen J, Hoischen A, Gilissen C, Mantere T*, Pylkäs K*. Exome sequencing identified rare recurrent copy number variants and hereditary breast cancer susceptibility. PLoS Genet. 2023;19(8):e1010889 *Shared Senior authorship

Kankuri-Tammilehto M, Tervasmäki A, Kraatari-Tiri M, Rahikkala E, Pylkäs K*, Kuismin O*. ATM c.7570G>C is a high-risk allele for breast cancer. Int J Cancer. 2023;152(3):429-435 *Shared Senior authorship

Koivuluoma S, Tervasmäki A, Kauppila S, Winqvist R, Kumpula T, Kuismin O, Moilanen J, Pylkäs K. Exome sequencing identifies a recurrent variant in SERPINA3 associating with hereditary susceptibility to breast cancer. Eur J Cancer. 2021:143:46-51.

Yang X, Leslie G, Doroszuk A, Schneider S, et al. Pylkäs K et al., Easton DF, Foulkes WD, Antoniou AC, Tischkowitz M. Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families. J Clin Oncol. 2020;38(7):674-685.

Tervasmäki A, Mantere T, Eshraghi L, Laurila N, Tuppurainen H, Ronkainen VP, Koivuluoma S, Devarajan R, Peltoketo H, Pylkäs K. Tumor suppressor MCPH1 regulates gene expression profiles related to malignant conversion and chromosomal assembly. Int J Cancer. 2019; 145(8):2070-2081.

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. PLoS Genet. 2016;12(1):e1005816.

Antoniou A, Casadei S, Heikkinen T, Barrowdale D, Pylkäs K, Roberts J et al., Foulkes WD, Tischkowitz M. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014;371:497-506

Nikkilä J*, Parplys AC*, Pylkäs K*, Bose M, Huo Y, Borgmann K, Rapakko K, Nieminen P, Xia B, Pospiech H, Winqvist R. Heterozygous mutations in PALB2 cause DNA replication and damage response defects. Nature Commun. 2013:4:2578. *Equal contribution

Pylkäs K, Vuorela M, Otsukka M, Kallioniemi A, Jukkola-Vuorinen A, Winqvist R. Rare copy number variants observed in hereditary breast cancer cases disrupt genes in estrogen signaling and TP53 tumor suppression network. PLoS Genet. 2012;8:e1002734.

Erkko H, Xia B, Nikkilä J, Schleutker J, Syrjäkoski K, Mannermaa A, Kallioniemi A, Pylkäs K, Karppinen SM, Rapakko K, Miron A, Sheng Q, Li G, Mattila H, Bell DW, Haber DA, Grip M, Reiman M, Jukkola-Vuorinen A, Mustonen A, Kere J, Aaltonen LA, Kosma VM, Kataja V, Soini Y, Drapkin RI, Livingston DM, Winqvist R. A recurrent mutation in PALB2 in Finnish cancer families. Nature 2007;446:316-9.