Summary
The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1–4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic features of gene amplification (e.g. double minutes [dmins] and homogeneously staining regions [HSRs]) [5–8]. As these and other chromosome regions are implicated in recurring abnormalities in breast cancer, it will become increasingly important to have band-or region-specific genomic libraries and probes in order to facilitate high resolution physical mapping and ultimately to clone breast cancer related genes [9]. Toward this end an important recent development in physical mapping has been the establishment of chromosome microdissection as a rapid and reproducible approach to rapidly isolate and characterize chromosome region-specific DNA, greatly facilitating the initial steps in positional cloning of disease-related genes [10–13]. In this brief report, we will highlight the application of chromosome microdissection to the generation of region-specific probes for both fluorescent in situ hybridization (FISH) and the generation of genomic microclone libraries. Additionally, efforts using this methodology to generate a microclone library encompassing the early onset breast/ovarian cancer (BRCA1) gene will be presented.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hainsworth P, Raphael K, Stilwell R, Bennett R, Garson O: Cytogenetic features of twenty-six primary breast cancers. Cancer Genet Cytogenet 52:205–218, 1991
Saint-Ruf C, Gerbault-Seureau M, Viegas-Pequignot E, Zafrani B, Malfoy B, Dutrillaux B: Recurrent homogeneously staining regions in 8pl in breast cancer and lack of amplification of POLB, LHRH, and PLAT genes. Cancer Genet Cytogenet 52:27–35, 1991
Thompson F, Emerson J, Dalton W, Yang J, McGee D, Villar H, Knox S, Massey K, Weinstein R, Bhattacharyya A, Trent J: Clonal chromosome abnormalities in human breast carcinomas, 1: Twentyeight cases with primary disease. Genes Chrom Cancer 7:185–193, 1993
Trent J, Yang J, Emerson J, Dalton W, McGee D, Massey K, Thompson F, Villar H: Clonal chromosome abnormalities in human breast carcinomas, II: Thirty-four cases with metastatic disease. Genes Chrom Cancer 7:194–203, 1993
Kellems R (ed): Gene Amplification in Mammalian Cells. Marcel Dekker, New York, 1993
Alitalo K, Schwab M: Oncogene amplification in tumor cells. Adv Cancer Res 47:235–281, 1986
Slamon D, Clark G, Wong S, Levin W, Ullrich A, McGuire W: Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182, 1987
Wahl G, Carroll S, Windle B: Cytogenetic and molecular dynamics of mammalian gene amplification: Evidence supporting chromosome breakage as an initiating event.In: Kellems, R (ed) Gene Amplification in Mammalian Cells. Marcel Dekker, New York, 1993, pp 513–532
Collins F: Positional cloning. Nature Genetics 1:3–8, 1992
Meltzer P, Guan XY, Burgess A, Trent J: Rapid generation of region specific probes by chromosome microdissection and their application. Nature Genetics 1:24–28, 1992
Guan XY, Trent J, Meltzer P: Generation of bandspecific painting probes from a single microdissected chromosome. Human Mol Gen 2:1117–1121, 1993
Guan XY, Meltzer P, Cao J, Trent J: Rapid generation of region-specific genomic clones by chromosome microdissection: Isolation of DNA from a region frequently deleted in malignant melanoma. Genomics 14:680–684, 1992
Zhang J, Trent J, Meltzer P: Rapid isolation and characterization of amplified DNA by chromosome microdissection: Identification of IGF1 R amplification in malignant melanoma. Oncogene 8:2827–2831, 1993
Heim S, Mitelman F: Cancer Cytogenetics. Alan R. Liss, New York, 1987
Mitelman F: Catalog of Chromosome Aberrations in Cancer, 4th Edition. Wiley-Liss, New York, 1992
Meltzer P, Guan X-Y, Trent J: Telomere capture stabilizes chromosome breakage. Nature Genetics 4:252–255, 1993
Pinkel D, Landegent J, Collins C, Fuscoe J, Segraves R, Lucas J, Gray J: Fluorescence in situ hybridization with human chromosome-specific libraries: Detection of trisomy 21 and translocations of chromosome 4. Proc Natl Acad Sci USA 85:9138–9141, 1988
Zhang J, Meltzer P, Jenkins R, Guan XY, Trent J: Application of chromosome microdissection probes for elucidation of BCR-ABL fusion variant Philadelphia chromosome translocations in chronic myelogenous leukemia. Blood 81:3365–3371, 1993
Guan XY, Meltzer P, Trent J: Rapid generation of whole chromosome painting probes (WCPs) by chromosome microdissection. Genomics 22:101–107, 1994
Weber BL, Abel KJ, Couch FJ, Merajver S, Castilla L, Brody LC, Collins FS: Transcript identification in the BRCA1 candidate region. Breast Cancer Res Treat (this issue)
Hall J, Lee M, Morrow J, Newman B, Anderson L, Huey B, King M: Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250: 1684–1689,1992
Abel K, Boehnke M, Prahalad M, Ho P, Flejter W, Watkins M, Vanderstoep J, Chandrasekharappa S, Collins F, Glover T, Weber B: A radiation hybrid map of the BRCA1 region of chromosome 17q12-q21. Genomics 17:632–641, 1993
Kallioniemi A, Kallioniemi OP, Waldman F, Chen L, Yu LC, Fung Smith H, Pinkel D, Gray J: Comparative genomic hybridization: A powerful new method for cytogenetic analysis of solid tumors. Science 258:818–820, 1991
Liang B, Meltzer P, Guan X-Y, Trent J: Genetic amplification elucidated by combined comparative genomic hybridization and chromosomal microdissection. Cancer Genet Cytogenet (in press)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Trent, J.M., Weber, B., Guan, X.Y. et al. Microdissection and microcloning of chromosomal alterations in human breast cancer. Breast Cancer Res Tr 33, 95–102 (1995). https://doi.org/10.1007/BF00682717
Issue Date:
DOI: https://doi.org/10.1007/BF00682717