No evidence of clonal somatic genetic alterations in cancer-associated fibroblasts from human breast and ovarian carcinomas.
There is increasing evidence showing that the stromal cells surrounding cancer epithelial cells, rather than being passive bystanders, might have a role in modifying tumor outgrowth. The molecular basis of this aspect of carcinoma etiology is controversial. Some studies have reported a high frequency of genetic aberrations in carcinoma-associated fibroblasts (CAFs), whereas other studies have reported very low or zero mutation rates. Resolution of this contentious area is of critical importance in terms of understanding both the basic biology of cancer as well as the potential clinical implications of CAF somatic alterations. We undertook genome-wide copy number and loss of heterozygosity (LOH) analysis of CAFs derived from breast and ovarian carcinomas using a 500K SNP array platform. Our data show conclusively that LOH and copy number alterations are extremely rare in CAFs and cannot be the basis of the carcinoma-promoting phenotypes of breast and ovarian CAFs.
Qiu
Wen
W
VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
Hu
Min
M
Sridhar
Anita
A
Opeskin
Ken
K
Fox
Stephen
S
Shipitsin
Michail
M
Trivett
Melanie
M
Thompson
Ella R
ER
Ramakrishna
Manasa
M
Gorringe
Kylie L
KL
Polyak
Kornelia
K
Haviv
Izhak
I
Campbell
Ian G
IG
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002999:Clone Cells / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D015894:Genome, Human; D006801:Humans; D019656:Loss of Heterozygosity; D042282:Microdissection; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D017154:Stromal Cells / Q000473:pathology