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Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair

  • Lao Saal
  • Sofia Gruvberger
  • Camilla Persson
  • Kristina Lövgren
  • Johan Staaf
  • Göran B Jönsson
  • MM Pires
  • Karolina Holm
  • Johan Vallon-Christersson
  • Håkan Olsson
  • Morten Krogh
  • Jorma Isola
  • Åke Borg
Publishing year: 2008
Language: English
Pages: 102-107
Publication/Series: Nature Genetics
Volume: 40
Issue: 1
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

Basal-like breast cancer (BBC) is a subtype of breast cancer with poor prognosis1, 2, 3. Inherited mutations of BRCA1, a cancer susceptibility gene involved in double-strand DNA break (DSB) repair, lead to breast cancers that are nearly always of the BBC subtype3, 4, 5; however, the precise molecular lesions and oncogenic consequences of BRCA1 dysfunction are poorly understood. Here we show that heterozygous inactivation of the tumor suppressor gene Pten leads to the formation of basal-like mammary tumors in mice, and that loss of PTEN expression is significantly associated with the BBC subtype in human sporadic and BRCA1-associated hereditary breast cancers. In addition, we identify frequent gross PTEN mutations, involving intragenic chromosome breaks, inversions, deletions and micro copy number aberrations, specifically in BRCA1-deficient tumors. These data provide an example of a specific and recurrent oncogenic consequence of BRCA1-dependent dysfunction in DNA repair and provide insight into the pathogenesis of BBC with therapeutic implications. These findings also argue that obtaining an accurate census of genes mutated in cancer will require a systematic examination for gross gene rearrangements, particularly in tumors with deficient DSB repair.


  • Cancer and Oncology


  • CREATE Health
  • Familial Breast Cancer
  • ISSN: 1546-1718
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