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BRCA1: mechanisms of inactivation and implications for management of patients.

The BRCA1 gene was cloned in 1994 as one of the genes that conferred genetic predisposition to early-onset breast and ovarian cancer. Since then, a genetic test for identification of high-risk individuals has been developed. Despite being implicated in many important cellular pathways, including DNA...

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Published in:Lancet Vol. 360; no. 9338; pp. 1007 - 1015
Main Authors: Kennedy RD, Quinn JE, Johnston PG, Harkin DP, Kennedy, Richard D, Quinn, Jennifer E, Johnston, Patrick G, Harkin, D Paul
Format: review tables/charts Journal Article
Published: Lancet 9/28/2002
Online Access:View this record in EBSCOhost
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      dt: 9/28/2002
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      pub: Lancet
      place: Philadelphia, Pennsylvania
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        10.1016/s0140-6736(02)11087-7
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        atl: BRCA1: mechanisms of inactivation and implications for management of patients.
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        au:
          Kennedy RD
          Quinn JE
          Johnston PG
          Harkin DP
          Kennedy, Richard D
          Quinn, Jennifer E
          Johnston, Patrick G
          Harkin, D Paul
        affil: Department of Oncology, Cancer Research Centre, Queen's University Belfast, BT9 7AB, Northern Ireland, Belfast, Ireland
      sug:
        subj:
          Breast Neoplasms Familial and Genetic
          Breast Neoplasms Prevention and Control
          Genes
          Genetic Screening
          Cancer Screening
          Family History
          Female
          Mutation
          Ovarian Neoplasms Familial and Genetic
          Tumor Markers, Biological
          Female
      ab: The BRCA1 gene was cloned in 1994 as one of the genes that conferred genetic predisposition to early-onset breast and ovarian cancer. Since then, a genetic test for identification of high-risk individuals has been developed. Despite being implicated in many important cellular pathways, including DNA repair and regulation of transcription, the exact mechanism by which inactivation of BRCA1 might lead to malignant transformation of cells remains unknown. We examine the mechanisms that underlie inactivation of BRCA1 and assess how they affect management of patients, in terms of both primary and secondary cancer prevention strategies. Furthermore, we look at the potential usefulness of BRCA1 as a prognostic tool and as a predictive marker of response to different classes of drugs. Finally, throughout this review, we draw links between the functional consequences of BRCA1 inactivation, in terms of key cellular signalling pathways, and how they might explain specific clinical observations in individuals who carry mutations in the gene.
      pubtype: Academic Journal
      doctype:
        review
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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