Cytogenetic heterogeneity and clonal evolution in synchronous bilateral breast carcinomas and their lymph node metastases from a male patient without any detectable BRCA2 germline mutation

Two synchronous bilateral breast carcinomas and their matched lymph node metastases from a 70-year-old man were cytogenetically analyzed. All four tumors were near-diploid, and except for the primary tumor from the right breast, had a 45,X,-Y clone in common. The loss of the Y chromosome rr as, however, common to all four tumors, whereas metaphase cells from peripheral blood lymphocytes showed a normal 46,XY chromosome complement. Th primary tumor from the right breast rr as monoclonal, with loss of the Y chromosome and gain of Iq, whereas its metastasis had two related clones: the 45,X, -Y clone, and the other a more complex version of the clone in the primary tumor, with inv(3), -14, and del(16)(q13) as additional changes. The primary tumor from the left breast was poly-clonal with three unrelated clones: 45,X,-Y/45,XY,-18/47,XY,+20, two of which rr ere present in its metastasis. DNA flow cytometric studies show ed diploidy for both primary tumors. No mutation in the BRCA2 gene was found on analysis of DNA from peripheral blood lymphocytes. The present findings show that del(16)(q13) is a recurrent finding among male breast carcinomas and that some of the primary cytogenetic abnormalities, as well as the pattern of chromosomal changes during the progression of sporadic breast carcinoma in the male, are similar to those in the female. In addition, the loss of the Y chromosome in the tumors but not in peripheral blood lymphocytes, suggests a possible role for this abnormality in the pathogenesis of male breast carcinoma. (C) Elsevier Science Inc., 2000. All rights reserved.