PMID- 11449404 OWN - NLM STAT- MEDLINE DCOM- 20010906 LR - 20191105 IS - 0196-4763 (Print) IS - 0196-4763 (Linking) VI - 46 IP - 3 DP - 2001 Jun 15 TI - Distinctive patterns of Her-2/neu, c-myc, and cyclin D1 gene amplification by fluorescence in situ hybridization in primary human breast cancers. PG - 136-49 AB - BACKGROUND: Human solid tumors undergo clonal evolution as they progress, but evidence for specific sequences of genetic changes that occur in individual tumors and are recapitulated in other tumors is difficult to obtain. METHODS: Patterns of amplification of Her-2/neu, c-myc, and cyclin D1 were determined by fluorescence in situ hybridization (FISH) in relation to the presence of p53 dysfunction and ploidy in 60 primary human breast cancers. RESULTS: We show that there are clusters of genophenotypic abnormalities that distinguish lobular breast cancers from nonlobular tumors; that cyclin D1 amplification occurs prior to the divergence of lobular breast cancers from nonlobular cancers; that p53 dysfunction, Her-2/neu amplification, and c-myc amplification are characteristic features of nonlobular breast cancers, but not of lobular breast cancers; and that the frequencies of amplification of all three oncogenes examined increase progressively with increasing aneuploidy, but that each gene exhibits a different profile of increasing amplification in relation to tumor progression. Early amplification of c-myc appears to be an especially prominent feature of hypertetraploid/hypertetrasomic tumors. CONCLUSIONS: The data suggest that in tumors containing multiple abnormalities, these abnormalities often accumulate in the same cells within each tumor. Furthermore, the same patterns of accumulation of multiple genophenotypic abnormalities are recapitulated in different tumors. FAU - Janocko, L E AU - Janocko LE AD - Department of Human Genetics MCP/Hahnemann University, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212, USA. FAU - Brown, K A AU - Brown KA FAU - Smith, C A AU - Smith CA FAU - Gu, L P AU - Gu LP FAU - Pollice, A A AU - Pollice AA FAU - Singh, S G AU - Singh SG FAU - Julian, T AU - Julian T FAU - Wolmark, N AU - Wolmark N FAU - Sweeney, L AU - Sweeney L FAU - Silverman, J F AU - Silverman JF FAU - Shackney, S E AU - Shackney SE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cytometry JT - Cytometry JID - 8102328 RN - 0 (Proto-Oncogene Proteins c-myc) RN - 136601-57-5 (Cyclin D1) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Alleles MH - Aneuploidy MH - Breast Neoplasms/*metabolism/*pathology MH - Carcinoma, Ductal, Breast MH - Chromosomes, Human, Pair 17 MH - Cyclin D1/*biosynthesis MH - Disease Progression MH - Genes, p53/genetics MH - Genotype MH - Humans MH - In Situ Hybridization, Fluorescence MH - Loss of Heterozygosity MH - Phenotype MH - Ploidies MH - Proto-Oncogene Proteins c-myc/*biosynthesis MH - Receptor, ErbB-2/*biosynthesis EDAT- 2001/07/13 10:00 MHDA- 2001/09/08 10:01 CRDT- 2001/07/13 10:00 PHST- 2001/07/13 10:00 [pubmed] PHST- 2001/09/08 10:01 [medline] PHST- 2001/07/13 10:00 [entrez] AID - 10.1002/cyto.1098 [pii] AID - 10.1002/cyto.1098 [doi] PST - ppublish SO - Cytometry. 2001 Jun 15;46(3):136-49. doi: 10.1002/cyto.1098.