Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair
Lao H. Saal,Sofia K. Gruvberger-Saal,Camilla Persson,Kristina Lövgren,Mervi Jumppanen,Johan Staaf,Göran Jönsson,Maira M. Pires,Matthew Maurer,Karolina Holm,Susan Koujak,Shivakumar Subramaniyam,Johan Vallon-Christersson,Håkan Olsson,Tao Su,Lorenzo Memeo,Thomas Ludwig,Stephen P. Ethier,Morten Krogh,Matthias Szabolcs,Vundavalli V. Murty,Jorma Isola,Hanina Hibshoosh,Ramon Parsons,Åke Borg +24 more
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It is shown 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.Abstract:
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 repairread more
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Comprehensive molecular portraits of human breast tumours
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References
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Molecular portraits of human breast tumours
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Therese Sørlie,Robert Tibshirani,Joel S. Parker,Trevor Hastie,James Stephen Marron,Andrew B. Nobel,Shibing Deng,Hilde Johnsen,Robert Pesich,Stephanie Geisler,Janos Demeter,Charles M. Perou,Per Eystein Lønning,Patrick O. Brown,Anne Lise Børresen-Dale,David Botstein +15 more
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PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer
Jing Li,Clifford Yen,Danny Liaw,Katrina Podsypanina,Shikha Bose,Steven I. Wang,Janusz Puc,Christa Miliaresis,Linda Rodgers,Richard W. McCombie,Sandra H. Bigner,Beppino C. Giovanella,Michael Ittmann,B. Tycko,Hanina Hibshoosh,Michael Wigler,Ramon Parsons +16 more
TL;DR: The PTEN product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions as discussed by the authors.
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Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer
Scott A. Tomlins,Daniel R. Rhodes,Sven Perner,Saravana M. Dhanasekaran,Rohit Mehra,Xiao-Wei Sun,Sooryanarayana Varambally,Xuhong Cao,Joelle Tchinda,Rainer Kuefer,Charles Lee,James E. Montie,Rajal B. Shah,Kenneth J. Pienta,Mark A. Rubin,Arul M. Chinnaiyan +15 more
TL;DR: In this article, the authors used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression and identified recurrent gene fusions of the 5' untranslated region of TMPRSS2 to ERG or ETV1.
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