A recurrent chromosome translocation breakpoint in breast and pancreatic cancer cell lines targets the neuregulin/NRG1 gene.
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.
Adélaïde
José
J
Département d'Oncologie Moléculaire, Laboratoires de Cytogénétique Moléculaire et de Pathologie Moléculaire, U119 Institut National de la Santé et de la Recherche Médicale (INSERM) and Institut Paoli-Calmettes (IPC), Marseille, France.
Huang
Huai-En
HE
Murati
Anne
A
Alsop
Amber E
AE
Orsetti
Béatrice
B
Mozziconacci
Marie-Joëlle
MJ
Popovici
Cornel
C
Ginestier
Christophe
C
Letessier
Anne
A
Basset
Céline
C
Courtay-Cahen
Céline
C
Jacquemier
Jocelyne
J
Theillet
Charles
C
Birnbaum
Daniel
D
Edwards
Paul A W
PA
Chaffanet
Max
M
D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D019457:Chromosome Breakage / Q000235:genetics*; D002874:Chromosome Mapping; D018387:Codon, Initiator / Q000235:genetics; D005091:Exons / Q000235:genetics; D006801:Humans; D020890:Neuregulin-1 / Q000096:biosynthesis / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D018387:Codon, Initiator; D020890:Neuregulin-1; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm