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Genome-wide analysis associates familial colorectal cancer with increases in copy number variations and a rare structural variation at 12p12.3

Yang, Rongxi; Chen, Bowang; Pfuetze, Katrin; Buch, Stephan; Steinke, Verena; Holinski-Feder, Elke; Stoecker, Sarah; von schoenfels, Witigo; Becker, Thomas and Schackert, Hans K., et al. (2014) In Carcinogenesis 35(2). p.315-323
Abstract
Colorectal cancer (CRC) is one of the most common cancer worldwide. However, a large number of genetic risk factors involved in CRC have not been understood. Copy number variations (CNVs) might partly contribute to the missing heritability of CRC. An increased overall burden of CNV has been identified in several complex diseases, whereas the association between the overall CNV burden and CRC risk is largely unknown. We performed a genome-wide investigation of CNVs on genomic DNA from 384 familial CRC cases and 1285 healthy controls by the Affymetrix 6.0 array. An increase of overall CNV burden was observed in familial CRC patients compared with healthy controls, especially for CNVs larger than 50kb (case/control ratio 1.66, P 0.025). In... (More)
Colorectal cancer (CRC) is one of the most common cancer worldwide. However, a large number of genetic risk factors involved in CRC have not been understood. Copy number variations (CNVs) might partly contribute to the missing heritability of CRC. An increased overall burden of CNV has been identified in several complex diseases, whereas the association between the overall CNV burden and CRC risk is largely unknown. We performed a genome-wide investigation of CNVs on genomic DNA from 384 familial CRC cases and 1285 healthy controls by the Affymetrix 6.0 array. An increase of overall CNV burden was observed in familial CRC patients compared with healthy controls, especially for CNVs larger than 50kb (case/control ratio 1.66, P 0.025). In addition, we discovered for the first time a novel structural variation at 12p12.3 and determined the breakpoints by strategic PCR and sequencing. This 12p12.3 structural variation was found in four of 2862 CRC cases but not in 6243 healthy controls (P 0.0098). RERGL gene (RERG/RAS-like), the only gene influenced by the 12p12.3 structural variation, sharing most of the conserved regions with its close family member RERG tumor suppressor gene (RAS-like, estrogen-regulated, growth inhibitor), might be a novel CRC-related gene. In conclusion, this is the first study to reveal the contribution of the overall burden of CNVs to familial CRC risk and identify a novel rare structural variation at 12p12.3 containing RERGL gene to be associated with CRC. (Less)
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Carcinogenesis
volume
35
issue
2
pages
315 - 323
publisher
Oxford University Press
external identifiers
  • wos:000331272100008
  • scopus:84893429973
ISSN
0143-3334
DOI
10.1093/carcin/bgt344
language
English
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yes
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b859780e-7e80-41e5-8562-b608db8dc3bb (old id 4368274)
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2014-04-07 09:20:32
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2017-11-12 03:12:44
@article{b859780e-7e80-41e5-8562-b608db8dc3bb,
  abstract     = {Colorectal cancer (CRC) is one of the most common cancer worldwide. However, a large number of genetic risk factors involved in CRC have not been understood. Copy number variations (CNVs) might partly contribute to the missing heritability of CRC. An increased overall burden of CNV has been identified in several complex diseases, whereas the association between the overall CNV burden and CRC risk is largely unknown. We performed a genome-wide investigation of CNVs on genomic DNA from 384 familial CRC cases and 1285 healthy controls by the Affymetrix 6.0 array. An increase of overall CNV burden was observed in familial CRC patients compared with healthy controls, especially for CNVs larger than 50kb (case/control ratio 1.66, P 0.025). In addition, we discovered for the first time a novel structural variation at 12p12.3 and determined the breakpoints by strategic PCR and sequencing. This 12p12.3 structural variation was found in four of 2862 CRC cases but not in 6243 healthy controls (P 0.0098). RERGL gene (RERG/RAS-like), the only gene influenced by the 12p12.3 structural variation, sharing most of the conserved regions with its close family member RERG tumor suppressor gene (RAS-like, estrogen-regulated, growth inhibitor), might be a novel CRC-related gene. In conclusion, this is the first study to reveal the contribution of the overall burden of CNVs to familial CRC risk and identify a novel rare structural variation at 12p12.3 containing RERGL gene to be associated with CRC.},
  author       = {Yang, Rongxi and Chen, Bowang and Pfuetze, Katrin and Buch, Stephan and Steinke, Verena and Holinski-Feder, Elke and Stoecker, Sarah and von schoenfels, Witigo and Becker, Thomas and Schackert, Hans K. and Royer-Pokora, Brigitte and Kloor, Matthias and Schmiegel, Wolff H. and Buettner, Reinhard and Engel, Christoph and Puertolas, Jesus Lascorz and Försti, Asta and Kunkel, Nelli and Bugert, Peter and Schreiber, Stefan and Krawczak, Michael and Schafmayer, Clemens and Propping, Peter and Hampe, Jochen and Hemminki, Kari and Burwinkel, Barbara},
  issn         = {0143-3334},
  language     = {eng},
  number       = {2},
  pages        = {315--323},
  publisher    = {Oxford University Press},
  series       = {Carcinogenesis},
  title        = {Genome-wide analysis associates familial colorectal cancer with increases in copy number variations and a rare structural variation at 12p12.3},
  url          = {http://dx.doi.org/10.1093/carcin/bgt344},
  volume       = {35},
  year         = {2014},
}