Distinct somatic genetic changes associated with tumor progression in carriers of BRCA1 and BRCA2 germ-line mutations

Tirkkonen, M (author)

Johannsson, O (author): Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine

Agnarsson, B A (author)

Olsson, Håkan (author): Lund University,Lunds universitet,Medicinsk onkologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumörmikromiljö,Institutionen för kliniska vetenskaper, Lund,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Medical oncology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Tumor microenvironment,Department of Clinical Sciences, Lund,Lund Melanoma Study Group,Lund University Research Groups

Ingvarsson, S (author): Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH

Karhu, R (author)

Tanner, M (author)

Isola, J (author): Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine

Barkardottir, R B (author)

Borg, Åke (author): Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine

Kallioniemi, O P (author)

(creator_code:org_t)

Abstract Subject headings

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.

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

By the author/editor: Tirkkonen, M; Johannsson, O; Agnarsson, B A; Olsson, Håkan; Ingvarsson, S; Karhu, R; show more...; Tanner, M; Isola, J; Barkardottir, R ...; Borg, Åke; Kallioniemi, O P; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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