A recurrent chromosome breakpoint in breast cancer at the NRG1/neuregulin 1/heregulin gene

Huang, Huai-En and Chin, Suet-Feung and Ginestier, Christophe and Bardou, Valérie-Jeanne and Adelaide, José and Iyer, N. Gopalakrishna and Garcia, Maria J. and Pole, Jessica C. and Callagy, Grace M. and Hewitt, Stephen M. and Gullick, William J. and Jacquemier, Jocelyne and Caldas, Carlos and Chaffanet, Max and Birnbaum, Daniel and Edwards, Paul A. (2004) A recurrent chromosome breakpoint in breast cancer at the NRG1/neuregulin 1/heregulin gene. Cancer Research, 64 (19). pp. 6840-6844. ISSN 0008-5472 . (Access to this publication is restricted)

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Abstract

Most studies of genomic rearrangements in common cancers have focused on regional gains and losses, but some rearrangements may break within specific genes. We previously reported that five breast cancer cell lines have chromosome translocations that break in the NRG1 gene and that could cause abnormal NRG1 expression. NRG1 encodes the Neuregulins 1 (formerly the Heregulins), ligands for members of the ErbB/epidermal growth factor-receptor family, which includes ErbB2/HER2. We have now screened for breaks at NRG1 in paraffin sections of breast tumors. Tissue microarrays were screened by fluorescence in situ hybridization, with hybridization probes proximal and distal to the expected breakpoints. This screen detects breaks but does not distinguish between translocation or deletion breakpoints. The screen was validated with array-comparative genomic hybridization on a custom 8p12 high-density genomic array to detect a lower copy number of the sequences that were lost distal to the breaks. We also precisely mapped the breaks in five tumors with different hybridization probes. Breaks in NRG1 were detected in 6% (19 of 323) of breast cancers and in some lung and ovarian cancers. In an unselected series of 213 cases with follow-up, breast cancers where the break was detected tended to be high-grade (65% grade III compared with 28% of negative cases). They were, like breast tumors in general, mainly ErbB2 low (11 of 13 were low) and estrogen receptor positive (11 of 13 positive).

Item Type: Article
Uncontrolled keywords: Breast Neoplasms/*genetics/metabolism Carcinoma, Ductal/genetics/metabolism Carcinoma, Lobular/genetics/metabolism Chromosome Breakage Chromosome Mapping Female Follow-Up Studies Gene Expression Humans In Situ Hybridization, Fluorescence Middle Aged Neuregulin-1/biosynthesis/*genetics Nucleic Acid Hybridization Oligonucleotide Array Sequence Analysis Paraffin Embedding
Subjects: Q Science
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences > Biomedical Research Group
Depositing User: Bill Gullick
Date Deposited: 04 Sep 2008 15:26
Last Modified: 02 May 2014 15:17
Resource URI: http://kar.kent.ac.uk/id/eprint/3977 (The current URI for this page, for reference purposes)
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