No evidence of clonal somatic genetic alterations in cancer-associated fibroblasts from human breast and ovarian carcinomas

Wen Qiu; Min Hu; Anita Sridhar; Ken Opeskin; Stephen Fox; Michail Shipitsin; Melanie Trivett; Ella R. Thompson; Manasa Ramakrishna; Kylie L. Gorringe; Kornelia Polyak; Izhak Haviv; Ian G. Campbell

doi:10.1038/ng.117

No evidence of clonal somatic genetic alterations in cancer-associated fibroblasts from human breast and ovarian carcinomas

Wen Qiu, Min Hu, Anita Sridhar, Ken Opeskin, Stephen Fox, Michail Shipitsin, Melanie Trivett, Ella R. Thompson, Manasa Ramakrishna, Kylie L. Gorringe, Kornelia Polyak, Izhak Haviv, Ian G. Campbell

Research output: Contribution to journal › Article › peer-review

248 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	650-655
Number of pages	6
Journal	Nature Genetics
Volume	40
Issue number	5
DOIs	https://doi.org/10.1038/ng.117
State	Published - May 2008
Externally published	Yes

Bibliographical note

Funding Information:
We thank the Peter MacCallum Cancer Centre Tissue Bank, and particularly L. Devereux, for their assistance in accessing tumor samples. We also thank the Peter MacCallum Cancer Centre Microarray and Bioinformatics core facilities for their assistance in the SNP array analysis. This work was supported by a grant (ID 400107) from the National Health and Medical Research Council of Australia (NHMRC). W.Q. is supported by NHMRC Dora Lush Postgraduate Scholarship. E.R.T. is supported by National Breast Cancer Foundation Postgraduate Scholarship. M.R. is supported by Melbourne Research Scholarship from University of Melbourne, Australia. I.H. is supported by US Department of Defense WXH1-1-06-0643 and the Komen for the Cure grants. This work was supported in part by US National Institutes of Health (CA116235) and American Cancer Society (RSG-05-154-01-MGO) grants to K.P.

Funding

We thank the Peter MacCallum Cancer Centre Tissue Bank, and particularly L. Devereux, for their assistance in accessing tumor samples. We also thank the Peter MacCallum Cancer Centre Microarray and Bioinformatics core facilities for their assistance in the SNP array analysis. This work was supported by a grant (ID 400107) from the National Health and Medical Research Council of Australia (NHMRC). W.Q. is supported by NHMRC Dora Lush Postgraduate Scholarship. E.R.T. is supported by National Breast Cancer Foundation Postgraduate Scholarship. M.R. is supported by Melbourne Research Scholarship from University of Melbourne, Australia. I.H. is supported by US Department of Defense WXH1-1-06-0643 and the Komen for the Cure grants. This work was supported in part by US National Institutes of Health (CA116235) and American Cancer Society (RSG-05-154-01-MGO) grants to K.P.

Funders	Funder number
NHMRC Dora Lush Postgraduate Scholarship
National Health and Medical Research Council of Australia
US Department of Defense	WXH1-1-06-0643
US National Institutes of Health	CA116235
American Cancer Society	RSG-05-154-01-MGO
National Cancer Institute	R01CA094074
Susan G. Komen for the Cure
National Breast Cancer Foundation
University of Melbourne

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.117

Cite this

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abstract = "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.",

author = "Wen Qiu and Min Hu and Anita Sridhar and Ken Opeskin and Stephen Fox and Michail Shipitsin and Melanie Trivett and Thompson, {Ella R.} and Manasa Ramakrishna and Gorringe, {Kylie L.} and Kornelia Polyak and Izhak Haviv and Campbell, {Ian G.}",

note = "Funding Information: We thank the Peter MacCallum Cancer Centre Tissue Bank, and particularly L. Devereux, for their assistance in accessing tumor samples. We also thank the Peter MacCallum Cancer Centre Microarray and Bioinformatics core facilities for their assistance in the SNP array analysis. This work was supported by a grant (ID 400107) from the National Health and Medical Research Council of Australia (NHMRC). W.Q. is supported by NHMRC Dora Lush Postgraduate Scholarship. E.R.T. is supported by National Breast Cancer Foundation Postgraduate Scholarship. M.R. is supported by Melbourne Research Scholarship from University of Melbourne, Australia. I.H. is supported by US Department of Defense WXH1-1-06-0643 and the Komen for the Cure grants. This work was supported in part by US National Institutes of Health (CA116235) and American Cancer Society (RSG-05-154-01-MGO) grants to K.P.",

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AU - Sridhar, Anita

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AU - Trivett, Melanie

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AU - Polyak, Kornelia

AU - Haviv, Izhak

AU - Campbell, Ian G.

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No evidence of clonal somatic genetic alterations in cancer-associated fibroblasts from human breast and ovarian carcinomas

Abstract

Bibliographical note

Funding

UN SDGs

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