Frequent met oncogene amplification in a Brca1/Trp53 mouse model of mammary tumorigenesis.
In a screen for gene copy number alterations in mouse mammary tumors initiated by loss of the Brca1 and Trp53 genes, we observed that the majority (11 of 15; 73%) had high-level amplification of wild-type Met, encoding a growth factor receptor implicated in tumor progression. Met amplification was localized to unstable double minute chromosomes and was uniquely found in mouse breast tumors driven by loss of Brca1 and Trp53. Whereas analogous MET amplification was not found in human breast cancers, the identification of a dominant somatic genetic lesion in the Brca1/Trp53 mouse model suggests that recurrent secondary hits may also exist in BRCA1-initiated human breast cancer.
Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, MA 02129, USA.
Gromoslaw A
GA
Smolen
Beth
B
Muir
Gayatry
G
Mohapatra
Anne
A
Barmettler
Woo J
WJ
Kim
Miguel N
MN
Rivera
Sara M
SM
Haserlat
Ross A
RA
Okimoto
Eunice
E
Kwak
Sonika
S
Dahiya
Judy E
JE
Garber
Daphne W
DW
Bell
Dennis C
DC
Sgroi
Lynda
L
Chin
Chu-Xia
CX
Deng
Daniel A
DA
Haber
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D019398:Genes, BRCA1; D008325:Mammary Neoplasms, Experimental / Q000235:genetics*; D051379:Mice; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; D019859:Proto-Oncogene Proteins c-met