Molecular cytogenetic analysis of breast cancer cell lines

Abstract

The extensive chromosome rearrangements of breast carcinomas must contribute to tumour development, but have been largely intractable to classical cytogenetic banding. We report here the analysis by 24-colour karyotyping and comparative genomic hybridization (CGH) of 19 breast carcinoma cell lines and one normal breast epithelial cell line, which provide model examples of karyotype patterns and translocations present in breast carcinomas. The CGH was compared with CGH of 106 primary breast cancers. The lines varied from perfectly diploid to highly aneuploid. Translocations were very varied and over 98% were unbalanced. The most frequent in the carcinomas were 8;11 in five lines; and 8;17, 1;4 and 1;10 in four lines. The most frequently involved chromosome was 8. Several lines showed complex multiply-translocated chromosomes. The very aneuploid karyotypes appeared to fall into two groups that evolved by different routes: one that steadily lost chromosomes and at one point doubled their entire karyotype; and another that steadily gained chromosomes, together with abnormalities. All karyotypes fell within the range seen in fresh material and CGH confirmed that the lines were broadly representative of fresh tumours. The karyotypes provide a resource for the cataloguing and analysis of translocations in these tumours, accessible at http://www.path.cam.ac.uk/~pawefish. © 2000 Cancer Research Campaign

Alternative transcripts of the candidate tumor suppressor gene, WWOX, are expressed at high levels in human breast tumors

“…We did not detect any homozygous deletions either in the breast tumors or in the breast cancer cell lines tested. In addition, all the breast cancer cell lines used in the present study have previously been shown by cytogenetic analysis to contain at least one normal chromosome 16 (Davidson et al, 2000). Even though we obtained an indication for an intragenic LOH in one of the cell lines analysed, this alteration is not expected to be su cient to explain the altered WWOX gene expression observed.…”

High-resolution analysis of chromosome rearrangements on 8p in breast, colon and pancreatic cancer reveals a complex pattern of loss, gain and translocation

“…Rearrangements of 8p were identified in a set of breast, colon and pancreatic cancer cell lines, for most of which we had previously obtained SKY (spectral karyotyping) karyotypes (Davidson et al, 2000;Abdel-Rahman et al, 2001;Sirivatanauksorn et al, 2001; available at http:// www.path.cam.ac.uk/Bpawefish).…”

“…Comparative genomic hybridization (CGH) also shows frequent losses of distal 8p in breast, colorectal, prostate, bladder and other cancers (e.g. Davidson et al, 2000;AbdelRahman et al, 2001;Karan et al, 2003;Hurst et al, 2004;Hwang et al, 2004), and more recently array CGH has begun to provide more detail of these losses (e.g. Paris et al, 2003;Douglas et al, 2004;Hurst et al, 2004;Nakao et al, 2004;Garcia et al, 2005).…”

“…In breast, for example, classical cytogenetic banding shows hsrs (homogeneously staining regions, i.e. large-scale amplifications) attached to 8p12 (Bernardino et al, 1998) and fluorescence in situ hybridization (FISH), CGH and Southern blotting show amplification generally in the region of 8p12 (Dib et al, 1995;Bautista and Theillet, 1998;Davidson et al, 2000), which often, but not invariably, includes FGFR1, and may occasionally extend as far distally as NRG1 (Ugolini et al, 1999). Recent array CGH studies that examine the 8p12 region in breast cancer have concentrated on the definition of the 8p12 amplicon (Ray et al, 2004;Garcia et al, 2005;Prentice et al, 2005).…”

Multicolour-banding fluorescence in situ hybridisation (mbanding-FISH) to identify recurrent chromosomal alterations in breast tumour cell lines

“…Chromosome 8 aberrations are very frequent in breast tumours, resulting in losses of 8p and gains of 8q (Mertens et al, 1995;Adeyinka et al, 2000;Davidson et al, 2000;Forozan et al, 2000;Kytölä et al, 2000;Höglund et al, 2001;Rummukainen et al, 2001;Struski et al, 2002;Teixeira et al, 2002;Ferti et al, 2004; Online CGH Tumour Database; http://cgap.nci.nih.gov/Chromosomes/ RecurrentAberrations). The 8p11 -p21 region contains several potential TSG and oncogenes (Adélaïde et al, 1998(Adélaïde et al, , 2003Ugolini et al, 1999;Conte et al, 2002;Ray et al, 2004).…”