Nature Communications publication:

Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors

From left: Jiqui Cheng, Hege Russnes, Ole Chr. Lingjærde and Peter Van Loo
From left: Jiqui Cheng, Hege Russnes, Ole Chr. Lingjærde and Peter Van Loo

The authors demonstrate the power of meta-analysis to identify rare somatic variants in cancer, and they identify several copy number alterations of potential importance for tumor development in those affected. The paper contributes to the understanding of the diversity of evolutionary processes in cancer.
The study, published online in Nature Communications on 31 October, is collaboration between OUS, UiO and several international partners. First author Jiqiu Cheng from the Hege Russnes group at the Department of Cancer Genetics at the Institute for Cancer Research. The senior author of the paper is Peter Van Loo at the Francis Crick Institute in UK.

Ordinarily, a gene is present in two copies in the human genome. Lacking both copies (called a homozygous deletion) is rare in cancer, but when it happens it often targets tumour suppressor genes. However, it can also occur in regions of increased genomic instability (fragile sites). Distinguishing between the two is non-trivial, and to solve the problem the authors developed a new statistical model and a computational tool. Based on the novel methodology, they systematically screened more than 2200 primary tumors across twelve cancer types. They were able to separate the regions with positive selection for homozygous deletions from the fragile sites, and found 16 established tumour suppressors as well as 27 candidate tumour suppressors. Several of these genes show prior evidence of a tumour suppressive function, while other candidate tumour suppressors are novel.

In summary, the authors demonstrate the power of meta-analysis to identify rare somatic variants in cancer, and they identify several copy number alterations of potential importance for tumor development in those affected. More generally, the paper contributes to the understanding of the diversity of evolutionary processes in cancer.

Links:

The article:

Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors.
Cheng J, Demeulemeester J, Wedge DC, Vollan HKM, Pitt JJ, Russnes HG, Pandey BP, Nilsen G, Nord S, Bignell GR, White KP, Børresen-Dale AL, Campbell PJ, Kristensen VN, Stratton MR, Lingjærde OC, Moreau Y, Loo PV.
Nat Commun. 2017 Oct 31;8(1):1221. doi: 10.1038/s41467-017-01355-0.
PMID: 29089486

Home page of the "Genomic alterations in breast cancer with impact on prognosis, therapy prediction and clinical follow-up" group, headed by Hege Russnes

About Ole Christian Lingjærde's research (from mn.uio.no)

Peter Van Loo's group Cancer Genomics Laboratory at The Francis Crick Institute