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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Molecular classification of breast carcinomas by comparative genomic hybridization: a specific somatic genetic profile for BRCA1 tumors.

In approximately 70% of the families with a high frequency of early-onset breast and/or ovarian cancer, BRCA1 or BRCA2 germline mutations cannot be identified with the current screening regime. Therefore, we used data mining to identify a somatic genetic signature to differentiate BRCA1 mutation carriers from non-BRCA1 carriers based on the genetic characteristics of their breast carcinomas. For this purpose, we developed a molecular classifier, which assigns a given tumor to either the BRCA1 or control group based on somatic genetic profiles as revealed by comparative genomic hybridization. This was performed on breast tumors selected from two groups of patients: 28 proven BRCA1 germline mutation carriers; and a control group consisting of 42 breast tumors from patients with unknown BRCA1 or BRCA2 status. We show that BRCA1 breast carcinomas exhibit specific somatic genetic aberrations and can be distinguished from control tumors with an accuracy of 84% (sensitivity of 96% and specificity of 76%). Chromosomal bands used by this classifier include regions on chromosomes 3p, 3q, and 5q. The classifier miss-assigned one patient with a BRCA1 mutation to the non-BRCA1 class. The germline mutation in this patient is a 62bp deletion in the last exon of BRCA1 (5622del62). Possibly, this mutation may give a different phenotypic effect than do mutations in other regions of the gene. Validation on an independent set of BRCA1 and sporadic tumors showed that the BRCA1 classifier correctly identified all 6 BRCA1 tumors and assigned 4 of the 19 control patients to the BRCA1 class. The resulting accuracy on the validation set is 84%.[1]

References

  1. Molecular classification of breast carcinomas by comparative genomic hybridization: a specific somatic genetic profile for BRCA1 tumors. Wessels, L.F., van Welsem, T., Hart, A.A., van't Veer, L.J., Reinders, M.J., Nederlof, P.M. Cancer Res. (2002) [Pubmed]
 
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