A recurrent chromosome translocation breakpoint in breast and pancreatic cancer cell lines targets the neuregulin/NRG1 gene

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Abstract
The 8p11–21 region is a frequent target of alterations in breast cancer and other carcinomas. We surveyed 34 breast tumor cell lines and 9 pancreatic cancer cell lines for alterations of this region by use of multicolor fluorescence in situ hybridization (M‐FISH) and BAC‐specific FISH. We describe a recurrent chromosome translocation breakpoint that targets the NRG1 gene on 8p12. NRG1 encodes growth factors of the neuregulin/heregulin‐1 family that are ligands for tyrosine kinase receptors of the ERBB family. Breakpoints within the NRG1 gene were found in four of the breast tumor cell lines: ZR‐75‐1, in a dic(8;11); HCC1937, in a t(8;10)(p12;p12.1); SUM‐52, in an hsr(8)(p12); UACC‐812, in a t(3;8); and in two of the pancreatic cancer cell lines: PaTu I, in a der(8)t(4;8); and SUIT‐2, in a del(8)(p). Mapping by two‐color FISH showed that the breaks were scattered over 1.1 Mb within the NRG1 gene. It is already known that the MDA‐MB‐175 breast tumor cell line has a dic(8;11), with a breakpoint in NRG1 that fuses NRG1 to the DOC4 gene on 11q13. Thus, we have found a total of seven breakpoints, in two types of cancer cell lines, that target the NRG1 gene. This suggests that the NRG1 locus is a recurring target of translocations in carcinomas. PCR analysis of reverse‐transcribed cell line RNAs revealed an extensive complexity of the NRG1 transcripts but failed to detect a consistent pattern of mRNA isoforms in the cell lines with NRG1 breakpoint.
Funding Information
  • Institut Paoli-Calmettes (IPC)
  • Institut National de la Sante et de la Recherche Medicale (INSERM)
  • Centre National de la Recherche Scientifique (CNRS)
  • Association pour la Recherche sur le Cancer
  • Cancer Research United Kingdom
  • Cambridge Commonwealth Trust
  • Keppel Foundation
  • Ministry of Research