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Case-control analysis of truncating mutations in DNA damage response genes connects TEX15 and FANCD2 with hereditary breast cancer susceptibility

  • Tuomo Mantere
  • Anna Tervasmäki
  • Anna Nurmi
  • Katrin Rapakko
  • Saila Kauppila
  • Jiangbo Tang
  • Johanna Schleutker
  • Anne Kallioniemi
  • Jaana M Hartikainen
  • Arto Mannermaa
  • Pentti Nieminen
  • Riitta Hanhisalo
  • Sini Lehto
  • Maija Suvanto
  • Mervi Grip
  • Arja Jukkola-Vuorinen
  • Maria Tengström
  • Päivi Auvinen
  • Anders Kvist
  • Åke Borg
  • Carl Blomqvist
  • Kristiina Aittomäki
  • Roger A. Greenberg
  • Robert Winqvist
  • Heli Nevanlinna
  • Katri Pylkäs
Publishing year: 2017-04-06
Language: English
Publication/Series: Scientific Reports
Volume: 7
Issue: 1
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

Several known breast cancer susceptibility genes encode proteins involved in DNA damage response (DDR) and are characterized by rare loss-of-function mutations. However, these explain less than half of the familial cases. To identify novel susceptibility factors, 39 rare truncating mutations, identified in 189 Northern Finnish hereditary breast cancer patients in parallel sequencing of 796 DDR genes, were studied for disease association. Mutation screening was performed for Northern Finnish breast cancer cases (n = 578-1565) and controls (n = 337-1228). Mutations showing potential cancer association were analyzed in additional Finnish cohorts. c.7253dupT in TEX15, encoding a DDR factor important in meiosis, associated with hereditary breast cancer (p = 0.018) and likely represents a Northern Finnish founder mutation. A deleterious c.2715 + 1G > A mutation in the Fanconi anemia gene, FANCD2, was over two times more common in the combined Finnish hereditary cohort compared to controls. A deletion (c.640-644del5) in RNF168, causative for recessive RIDDLE syndrome, had high prevalence in majority of the analyzed cohorts, but did not associate with breast cancer. In conclusion, truncating variants in TEX15 and FANCD2 are potential breast cancer risk factors, warranting further investigations in other populations. Furthermore, high frequency of RNF168 c.640-644del5 indicates the need for its testing in Finnish patients with RIDDLE syndrome symptoms.


  • Cancer and Oncology
  • Medical Genetics


  • ISSN: 2045-2322
Åke Borg
Åke Borg
E-mail: ake [dot] borg [at] med [dot] lu [dot] se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2


Project manager

Familial Breast Cancer



Oncology and Pathology, MV

MV 404 C21C2