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Articles

Distinct Somatic Genetic Changes Associated with Tumor Progression in Carriers of BRCA1 and BRCA2 Germ-line Mutations

Mika Tirkkonen, Oskar Johannsson, Bjarni A. Agnarsson, Håkan Olsson, Sigurdur Ingvarsson, Ritva Karhu, Minna Tanner, Jorma Isola, Rosa B. Barkardottir, Åke Borg and Olli-P. Kallioniemi
Mika Tirkkonen
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Oskar Johannsson
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Bjarni A. Agnarsson
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Håkan Olsson
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Sigurdur Ingvarsson
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Ritva Karhu
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Minna Tanner
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Jorma Isola
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Rosa B. Barkardottir
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Åke Borg
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Olli-P. Kallioniemi
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DOI:  Published April 1997
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Abstract

BRCA1 and BRCA2 mutations confer increased risk for development of breast cancer, but a number of additional, currently largely unknown, somatic genetic defects must also accumulate in the breast epithelial cells before malignancy develops. To evaluate the nature of these additional somatic genetic defects, we performed a genome-wide survey by comparative genomic hybridization on breast cancers from 21 BRCA1 mutation carriers, 15 BRCA2 mutation carriers, and 55 unselected controls. The total number of genetic changes was almost two times higher in tumors from both BRCA1 and BRCA2 mutation carriers than in the control group. In BRCA1 tumors, losses of 5q (86%), 4q (81%), 4p (64%), 2q (40%), and 12q (40%) were significantly more common than in the control group (7–13%). BRCA2 tumors were characterized by a higher frequency of 13q (73%) and 6q (60%) losses and gains of 17q22-q24 (87%) and 20q13 (60%) as compared to the prevalence of these changes in the control group (12–18%). In conclusion, accumulation of somatic genetic changes during tumor progression may follow a unique pathway in individuals genetically predisposed to cancer, especially by the BRCA1 gene. Activation or loss of genes in the affected chromosomal regions may be selected for during tumor progression in cells lacking functional BRCA1 or BRCA2. Identification of such genes could provide targets for therapeutic intervention and early diagnosis.

Footnotes

  • ↵1 This study was supported by the Finnish Science Academy, Sigrid Juselius Foundation, Finnish Cancer Society, Tampere University Hospital Fund, Nordic Cancer Union Fund, Swedish Cancer Society, GAE Nilsson's Foundation, and B. Kamprad's Foundation. In addition, M. T. was supported by personal grants from the Pirkanmaa Cancer Society, as well as Finnish and Pirkanmaa Cultural Foundations.

  • ↵2 To whom requests for reprints should be addressed. Phone: (301) 435-2896; Fax: (301) 402-7957; E-mail: okalli@nchgr.nih.gov.

  • Received November 26, 1996.
  • Accepted February 14, 1997.
  • ©1997 American Association for Cancer Research.
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April 1997
Volume 57, Issue 7
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Distinct Somatic Genetic Changes Associated with Tumor Progression in Carriers of BRCA1 and BRCA2 Germ-line Mutations
Mika Tirkkonen, Oskar Johannsson, Bjarni A. Agnarsson, Håkan Olsson, Sigurdur Ingvarsson, Ritva Karhu, Minna Tanner, Jorma Isola, Rosa B. Barkardottir, Åke Borg and Olli-P. Kallioniemi
Cancer Res April 1 1997 (57) (7) 1222-1227;

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Distinct Somatic Genetic Changes Associated with Tumor Progression in Carriers of BRCA1 and BRCA2 Germ-line Mutations
Mika Tirkkonen, Oskar Johannsson, Bjarni A. Agnarsson, Håkan Olsson, Sigurdur Ingvarsson, Ritva Karhu, Minna Tanner, Jorma Isola, Rosa B. Barkardottir, Åke Borg and Olli-P. Kallioniemi
Cancer Res April 1 1997 (57) (7) 1222-1227;
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