Overexpression of BRCA2 gene in sporadic breast tumours.
The breast cancer susceptibility gene BRCA2 is expressed in a wide range of tissues as an 11-kb mRNA transcript that encodes a 3418-amino acid protein involved in the response to DNA damage. To obtain better a molecular characterization of BRCA2 expression in sporadic breast cancer, we quantified BRCA2 mRNA by means of RT - PCR in a large series of human primary breast tumours. BRCA2 expression showed wide variations in tumour tissues, being underexpressed in 14/127 (11%) and overexpressed in 25/127 (20%). BRCA2 overexpression (but not underexpression) correlated significantly with Scarff, Bloom and Richardson (SBR) histopathological grade III (P=0.007) and was mainly attributed to nuclear polymorphism (P=0.005) and mitotic index (P=0.048), suggesting that the BRCA2 gene contributes to the proliferation rate in breast tumours. BRCA2 status (under and/or overexpression versus normal expression) was not associated with subsequent relapse and with significantly shorter disease-free survival. The observed disruption of BRCA2 expression is not due to allelic loss, because the latter did not correlate with altered BRCA2 mRNA expression in our tumour series. Taken together, these data suggest the involvement, especially by overexpression, of the BRCA2 gene in sporadic breast tumours, and the existence of another important tumour-suppressor gene in breast cancer, in the 13q12-q13 region.
Bièche
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Laboratoire d'Oncogénétique, Centre René Huguenin, 35 rue Dailly, F-92211 St-Cloud, France.
Noguès
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C
Lidereau
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R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000648:ultrastructure; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics / Q000648:ultrastructure; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008593:Menopause; D018895:Microsatellite Repeats; D008875:Middle Aged; D008940:Mitotic Index; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D024682:BRCA2 Protein; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors