Contribution of allelic imbalance to colorectal cancer

Palin, Kimmo,University of Helsinki; Pitkänen, Esa,University of Helsinki; Turunen, Mikko,University of Helsinki; Sahu, Biswajyoti,University of Helsinki; Pihlajamaa, Päivi,University of Helsinki; Kivioja, Teemu,University of Helsinki; Kaasinen, Eevi,Karolinska Institute; Välimäki, Niko,University of Helsinki; Hänninen, Ulrika,University of Helsinki; Cajuso, Tatiana,University of Helsinki; Aavikko, Mervi,University of Helsinki; Tuupanen, Sari,University of Helsinki; Kilpivaara, Outi,University of Helsinki; van den Berg, Linda,University of Helsinki; Kondelin, Johanna,University of Helsinki; Tanskanen, Tomas,University of Helsinki; Katainen, Riku,University of Helsinki; Grau, Marta,University of Helsinki; Rauanheimo, Heli,University of Helsinki; Plaketti, Roosa-Maria,University of Helsinki; Taira, Aurora,University of Helsinki; Sulo, Päivi,University of Helsinki; Hartonen, Tuomo,University of Helsinki; Dave, Kashyap,Karolinska Institute; Schmierer, Bernhard,Karolinska Institute; Botla, Sandeep,Karolinska Institute; Sokolova, Maria,University of Helsinki; Vähärautio, Anna,University of Helsinki; Gladysz, Kornelia,University of Helsinki; Ongen, Halit,University of Geneva; Dermitzakis, Emmanouil,University of Geneva; Bramsen, Jesper,Aarhus University Hospital; Ørntoft, Torben,Aarhus University Hospital; Lindbjerg Andersen, Claus,Aarhus University Hospital; Ristimäki, Ari,University of Helsinki; Lepistö, Anna,Helsinki University Hospital; Renkonen-Sinisalo, Laura,Helsinki University Hospital; Mecklin, Jukka-Pekka,Jyväskylä Central Hospital and University of Eastern Finland; Taipale, Jussi,University of Helsinki, Karolinska Institute; Aaltonen, Lauri,University of Helsinki

Date

2018-09-07

Author(s)

Palin, Kimmo,University of Helsinki

Pitkänen, Esa,University of Helsinki

Turunen, Mikko,University of Helsinki

Sahu, Biswajyoti,University of Helsinki

Pihlajamaa, Päivi,University of Helsinki

Kivioja, Teemu,University of Helsinki

Kaasinen, Eevi,Karolinska Institute

Välimäki, Niko,University of Helsinki

Hänninen, Ulrika,University of Helsinki

Cajuso, Tatiana,University of Helsinki

Aavikko, Mervi,University of Helsinki

Tuupanen, Sari,University of Helsinki

Kilpivaara, Outi,University of Helsinki

van den Berg, Linda,University of Helsinki

Kondelin, Johanna,University of Helsinki

Tanskanen, Tomas,University of Helsinki

Katainen, Riku,University of Helsinki

Grau, Marta,University of Helsinki

Rauanheimo, Heli,University of Helsinki

Plaketti, Roosa-Maria,University of Helsinki

Taira, Aurora,University of Helsinki

Sulo, Päivi,University of Helsinki

Hartonen, Tuomo,University of Helsinki

Dave, Kashyap,Karolinska Institute

Schmierer, Bernhard,Karolinska Institute

Botla, Sandeep,Karolinska Institute

Sokolova, Maria,University of Helsinki

Vähärautio, Anna,University of Helsinki

Gladysz, Kornelia,University of Helsinki

Ongen, Halit,University of Geneva

Dermitzakis, Emmanouil,University of Geneva

Bramsen, Jesper,Aarhus University Hospital

Ørntoft, Torben,Aarhus University Hospital

Lindbjerg Andersen, Claus,Aarhus University Hospital

Ristimäki, Ari,University of Helsinki

Lepistö, Anna,Helsinki University Hospital

Renkonen-Sinisalo, Laura,Helsinki University Hospital

Mecklin, Jukka-Pekka,Jyväskylä Central Hospital and University of Eastern Finland

Taipale, Jussi,University of Helsinki, Karolinska Institute

Aaltonen, Lauri,University of Helsinki

Unique identifier

10.5281/zenodo.1222172

Metadata

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Research data

Citation

Palin, Kimmo,University of Helsinki. Pitkänen, Esa,University of Helsinki. Turunen, Mikko,University of Helsinki. Sahu, Biswajyoti,University of Helsinki. Pihlajamaa, Päivi,University of Helsinki. Kivioja, Teemu,University of Helsinki. Kaasinen, Eevi,Karolinska Institute. Välimäki, Niko,University of Helsinki. Hänninen, Ulrika,University of Helsinki. Cajuso, Tatiana,University of Helsinki. Aavikko, Mervi,University of Helsinki. Tuupanen, Sari,University of Helsinki. Kilpivaara, Outi,University of Helsinki. van den Berg, Linda,University of Helsinki. Kondelin, Johanna,University of Helsinki. Tanskanen, Tomas,University of Helsinki. Katainen, Riku,University of Helsinki. Grau, Marta,University of Helsinki. Rauanheimo, Heli,University of Helsinki. Plaketti, Roosa-Maria,University of Helsinki. Taira, Aurora,University of Helsinki. Sulo, Päivi,University of Helsinki. Hartonen, Tuomo,University of Helsinki. Dave, Kashyap,Karolinska Institute. Schmierer, Bernhard,Karolinska Institute. Botla, Sandeep,Karolinska Institute. Sokolova, Maria,University of Helsinki. Vähärautio, Anna,University of Helsinki. Gladysz, Kornelia,University of Helsinki. Ongen, Halit,University of Geneva. Dermitzakis, Emmanouil,University of Geneva. Bramsen, Jesper,Aarhus University Hospital. Ørntoft, Torben,Aarhus University Hospital. Lindbjerg Andersen, Claus,Aarhus University Hospital. Ristimäki, Ari,University of Helsinki. Lepistö, Anna,Helsinki University Hospital. Renkonen-Sinisalo, Laura,Helsinki University Hospital. Mecklin, Jukka-Pekka,Jyväskylä Central Hospital and University of Eastern Finland. Taipale, Jussi,University of Helsinki, Karolinska Institute. Aaltonen, Lauri,University of Helsinki. , Contribution of allelic imbalance to colorectal cancer, 2018, 10.5281/zenodo.1222172.

Abstract

Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge, and unbiased CRISPR-Cas9 knockout and activation screens identified altogether 79 genes within AI peaks regulating cell growth. Genetic and functional data implicates loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.