Loading…

Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer

Colorectal cancer (CRC) is characterized by specific patterns of copy number alterations (CNAs), which helped with the identification of driver oncogenes and tumor suppressor genes (TSGs). More recently, the usage of single nucleotide polymorphism arrays provided information of copy number neutral l...

Full description

Saved in:
Bibliographic Details
Published in:Carcinogenesis (New York) 2015-10, Vol.36 (10), p.1103-1110
Main Authors: Torabi, Keyvan, Miró, Rosa, Fernández-Jiménez, Nora, Quintanilla, Isabel, Ramos, Laia, Prat, Esther, del Rey, Javier, Pujol, Núria, Killian, J Keith, Meltzer, Paul S, Fernández, Pedro Luis, Ried, Thomas, Lozano, Juan José, Camps, Jordi, Ponsa, Immaculada
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c486t-83c0807739ed889194fe44187103427c2fcfb5c3bb99f1c684ee8033a549c08f3
cites cdi_FETCH-LOGICAL-c486t-83c0807739ed889194fe44187103427c2fcfb5c3bb99f1c684ee8033a549c08f3
container_end_page 1110
container_issue 10
container_start_page 1103
container_title Carcinogenesis (New York)
container_volume 36
creator Torabi, Keyvan
Miró, Rosa
Fernández-Jiménez, Nora
Quintanilla, Isabel
Ramos, Laia
Prat, Esther
del Rey, Javier
Pujol, Núria
Killian, J Keith
Meltzer, Paul S
Fernández, Pedro Luis
Ried, Thomas
Lozano, Juan José
Camps, Jordi
Ponsa, Immaculada
description Colorectal cancer (CRC) is characterized by specific patterns of copy number alterations (CNAs), which helped with the identification of driver oncogenes and tumor suppressor genes (TSGs). More recently, the usage of single nucleotide polymorphism arrays provided information of copy number neutral loss of heterozygosity, thus suggesting the occurrence of somatic uniparental disomy (UPD) and uniparental polysomy (UPP) events. The aim of this study is to establish an integrative profiling of recurrent UPDs/UPPs and CNAs in sporadic CRC. Our results indicate that regions showing high frequencies of UPD/UPP mostly coincide with regions typically involved in genomic losses. Among them, chromosome arms 3p, 5q, 9q, 10q, 14q, 17p, 17q, 20p, 21q and 22q preferentially showed UPDs/UPPs over genomic losses suggesting that tumor cells must maintain the disomic state of certain genes to favor cellular fitness. A meta-analysis using over 300 samples from The Cancer Genome Atlas confirmed our findings. Several regions affected by recurrent UPDs/UPPs contain well-known TSGs, as well as novel candidates such as ARID1A, DLC1, TCF7L2 and DMBT1. In addition, VCAN, FLT4, SFRP1 and GAS7 were also frequently involved in regions of UPD/UPP and displayed high levels of methylation. Finally, sequencing and fluorescence in situ hybridization analysis of the gene APC underlined that a somatic UPD event might represent the second hit to achieve biallelic inactivation of this TSG in colorectal tumors. In summary, our data define a profile of somatic UPDs/UPPs in sporadic CRC and highlights the importance of these events as a mechanism to achieve the inactivation of TSGs.
doi_str_mv 10.1093/carcin/bgv115
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4598814</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1727681370</sourcerecordid><originalsourceid>FETCH-LOGICAL-c486t-83c0807739ed889194fe44187103427c2fcfb5c3bb99f1c684ee8033a549c08f3</originalsourceid><addsrcrecordid>eNpVUU1v1DAQtRCIbheOvSIfuaT1ZJzEviBVVaFIleAAZ8vxjhdXiR3sZKX996TaUrWn-Xrz5mkeYxcgLkFovHI2uxCv-v0BoHnDNiBbUdWgxFu2ESCxQkR5xs5LeRACWmz0e3ZWt7VEBNgw-9POM-VYePK8pNHOwfElhslmirMd-C6s3SMPu7UM_shjOtDA52VMmZdlmjKVsqZ7ilR4iNylIWVyj6vORkf5A3vn7VDo41Pcst9fb3_d3FX3P759v7m-r5xU7VwpdEKJrkNNO6U0aOlJSlAdCJR152rvfN847HutPbhWSSIlEG0j9brpccu-nHinpR9p51a92Q5mymG0-WiSDeb1JIY_Zp8ORjZaqfVTW_b5iSCnvwuV2YyhOBoGGyktxUBXd60C7MQKrU5Ql1MpmfzzGRDm0RZzssWcbFnxn15qe0b_9wH_AdkbjaA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1727681370</pqid></control><display><type>article</type><title>Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer</title><source>Oxford Journals Online</source><creator>Torabi, Keyvan ; Miró, Rosa ; Fernández-Jiménez, Nora ; Quintanilla, Isabel ; Ramos, Laia ; Prat, Esther ; del Rey, Javier ; Pujol, Núria ; Killian, J Keith ; Meltzer, Paul S ; Fernández, Pedro Luis ; Ried, Thomas ; Lozano, Juan José ; Camps, Jordi ; Ponsa, Immaculada</creator><creatorcontrib>Torabi, Keyvan ; Miró, Rosa ; Fernández-Jiménez, Nora ; Quintanilla, Isabel ; Ramos, Laia ; Prat, Esther ; del Rey, Javier ; Pujol, Núria ; Killian, J Keith ; Meltzer, Paul S ; Fernández, Pedro Luis ; Ried, Thomas ; Lozano, Juan José ; Camps, Jordi ; Ponsa, Immaculada</creatorcontrib><description>Colorectal cancer (CRC) is characterized by specific patterns of copy number alterations (CNAs), which helped with the identification of driver oncogenes and tumor suppressor genes (TSGs). More recently, the usage of single nucleotide polymorphism arrays provided information of copy number neutral loss of heterozygosity, thus suggesting the occurrence of somatic uniparental disomy (UPD) and uniparental polysomy (UPP) events. The aim of this study is to establish an integrative profiling of recurrent UPDs/UPPs and CNAs in sporadic CRC. Our results indicate that regions showing high frequencies of UPD/UPP mostly coincide with regions typically involved in genomic losses. Among them, chromosome arms 3p, 5q, 9q, 10q, 14q, 17p, 17q, 20p, 21q and 22q preferentially showed UPDs/UPPs over genomic losses suggesting that tumor cells must maintain the disomic state of certain genes to favor cellular fitness. A meta-analysis using over 300 samples from The Cancer Genome Atlas confirmed our findings. Several regions affected by recurrent UPDs/UPPs contain well-known TSGs, as well as novel candidates such as ARID1A, DLC1, TCF7L2 and DMBT1. In addition, VCAN, FLT4, SFRP1 and GAS7 were also frequently involved in regions of UPD/UPP and displayed high levels of methylation. Finally, sequencing and fluorescence in situ hybridization analysis of the gene APC underlined that a somatic UPD event might represent the second hit to achieve biallelic inactivation of this TSG in colorectal tumors. In summary, our data define a profile of somatic UPDs/UPPs in sporadic CRC and highlights the importance of these events as a mechanism to achieve the inactivation of TSGs.</description><identifier>ISSN: 0143-3334</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/bgv115</identifier><identifier>PMID: 26243311</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Chromosome Aberrations ; Colorectal Neoplasms - complications ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; Genes, Tumor Suppressor ; Humans ; Loss of Heterozygosity ; Original Manuscript ; Uniparental Disomy - genetics ; Uniparental Disomy - pathology</subject><ispartof>Carcinogenesis (New York), 2015-10, Vol.36 (10), p.1103-1110</ispartof><rights>The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</rights><rights>The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-83c0807739ed889194fe44187103427c2fcfb5c3bb99f1c684ee8033a549c08f3</citedby><cites>FETCH-LOGICAL-c486t-83c0807739ed889194fe44187103427c2fcfb5c3bb99f1c684ee8033a549c08f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26243311$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Torabi, Keyvan</creatorcontrib><creatorcontrib>Miró, Rosa</creatorcontrib><creatorcontrib>Fernández-Jiménez, Nora</creatorcontrib><creatorcontrib>Quintanilla, Isabel</creatorcontrib><creatorcontrib>Ramos, Laia</creatorcontrib><creatorcontrib>Prat, Esther</creatorcontrib><creatorcontrib>del Rey, Javier</creatorcontrib><creatorcontrib>Pujol, Núria</creatorcontrib><creatorcontrib>Killian, J Keith</creatorcontrib><creatorcontrib>Meltzer, Paul S</creatorcontrib><creatorcontrib>Fernández, Pedro Luis</creatorcontrib><creatorcontrib>Ried, Thomas</creatorcontrib><creatorcontrib>Lozano, Juan José</creatorcontrib><creatorcontrib>Camps, Jordi</creatorcontrib><creatorcontrib>Ponsa, Immaculada</creatorcontrib><title>Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>Colorectal cancer (CRC) is characterized by specific patterns of copy number alterations (CNAs), which helped with the identification of driver oncogenes and tumor suppressor genes (TSGs). More recently, the usage of single nucleotide polymorphism arrays provided information of copy number neutral loss of heterozygosity, thus suggesting the occurrence of somatic uniparental disomy (UPD) and uniparental polysomy (UPP) events. The aim of this study is to establish an integrative profiling of recurrent UPDs/UPPs and CNAs in sporadic CRC. Our results indicate that regions showing high frequencies of UPD/UPP mostly coincide with regions typically involved in genomic losses. Among them, chromosome arms 3p, 5q, 9q, 10q, 14q, 17p, 17q, 20p, 21q and 22q preferentially showed UPDs/UPPs over genomic losses suggesting that tumor cells must maintain the disomic state of certain genes to favor cellular fitness. A meta-analysis using over 300 samples from The Cancer Genome Atlas confirmed our findings. Several regions affected by recurrent UPDs/UPPs contain well-known TSGs, as well as novel candidates such as ARID1A, DLC1, TCF7L2 and DMBT1. In addition, VCAN, FLT4, SFRP1 and GAS7 were also frequently involved in regions of UPD/UPP and displayed high levels of methylation. Finally, sequencing and fluorescence in situ hybridization analysis of the gene APC underlined that a somatic UPD event might represent the second hit to achieve biallelic inactivation of this TSG in colorectal tumors. In summary, our data define a profile of somatic UPDs/UPPs in sporadic CRC and highlights the importance of these events as a mechanism to achieve the inactivation of TSGs.</description><subject>Chromosome Aberrations</subject><subject>Colorectal Neoplasms - complications</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Genes, Tumor Suppressor</subject><subject>Humans</subject><subject>Loss of Heterozygosity</subject><subject>Original Manuscript</subject><subject>Uniparental Disomy - genetics</subject><subject>Uniparental Disomy - pathology</subject><issn>0143-3334</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNpVUU1v1DAQtRCIbheOvSIfuaT1ZJzEviBVVaFIleAAZ8vxjhdXiR3sZKX996TaUrWn-Xrz5mkeYxcgLkFovHI2uxCv-v0BoHnDNiBbUdWgxFu2ESCxQkR5xs5LeRACWmz0e3ZWt7VEBNgw-9POM-VYePK8pNHOwfElhslmirMd-C6s3SMPu7UM_shjOtDA52VMmZdlmjKVsqZ7ilR4iNylIWVyj6vORkf5A3vn7VDo41Pcst9fb3_d3FX3P759v7m-r5xU7VwpdEKJrkNNO6U0aOlJSlAdCJR152rvfN847HutPbhWSSIlEG0j9brpccu-nHinpR9p51a92Q5mymG0-WiSDeb1JIY_Zp8ORjZaqfVTW_b5iSCnvwuV2YyhOBoGGyktxUBXd60C7MQKrU5Ql1MpmfzzGRDm0RZzssWcbFnxn15qe0b_9wH_AdkbjaA</recordid><startdate>20151001</startdate><enddate>20151001</enddate><creator>Torabi, Keyvan</creator><creator>Miró, Rosa</creator><creator>Fernández-Jiménez, Nora</creator><creator>Quintanilla, Isabel</creator><creator>Ramos, Laia</creator><creator>Prat, Esther</creator><creator>del Rey, Javier</creator><creator>Pujol, Núria</creator><creator>Killian, J Keith</creator><creator>Meltzer, Paul S</creator><creator>Fernández, Pedro Luis</creator><creator>Ried, Thomas</creator><creator>Lozano, Juan José</creator><creator>Camps, Jordi</creator><creator>Ponsa, Immaculada</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20151001</creationdate><title>Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer</title><author>Torabi, Keyvan ; Miró, Rosa ; Fernández-Jiménez, Nora ; Quintanilla, Isabel ; Ramos, Laia ; Prat, Esther ; del Rey, Javier ; Pujol, Núria ; Killian, J Keith ; Meltzer, Paul S ; Fernández, Pedro Luis ; Ried, Thomas ; Lozano, Juan José ; Camps, Jordi ; Ponsa, Immaculada</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-83c0807739ed889194fe44187103427c2fcfb5c3bb99f1c684ee8033a549c08f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Chromosome Aberrations</topic><topic>Colorectal Neoplasms - complications</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Genes, Tumor Suppressor</topic><topic>Humans</topic><topic>Loss of Heterozygosity</topic><topic>Original Manuscript</topic><topic>Uniparental Disomy - genetics</topic><topic>Uniparental Disomy - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Torabi, Keyvan</creatorcontrib><creatorcontrib>Miró, Rosa</creatorcontrib><creatorcontrib>Fernández-Jiménez, Nora</creatorcontrib><creatorcontrib>Quintanilla, Isabel</creatorcontrib><creatorcontrib>Ramos, Laia</creatorcontrib><creatorcontrib>Prat, Esther</creatorcontrib><creatorcontrib>del Rey, Javier</creatorcontrib><creatorcontrib>Pujol, Núria</creatorcontrib><creatorcontrib>Killian, J Keith</creatorcontrib><creatorcontrib>Meltzer, Paul S</creatorcontrib><creatorcontrib>Fernández, Pedro Luis</creatorcontrib><creatorcontrib>Ried, Thomas</creatorcontrib><creatorcontrib>Lozano, Juan José</creatorcontrib><creatorcontrib>Camps, Jordi</creatorcontrib><creatorcontrib>Ponsa, Immaculada</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Torabi, Keyvan</au><au>Miró, Rosa</au><au>Fernández-Jiménez, Nora</au><au>Quintanilla, Isabel</au><au>Ramos, Laia</au><au>Prat, Esther</au><au>del Rey, Javier</au><au>Pujol, Núria</au><au>Killian, J Keith</au><au>Meltzer, Paul S</au><au>Fernández, Pedro Luis</au><au>Ried, Thomas</au><au>Lozano, Juan José</au><au>Camps, Jordi</au><au>Ponsa, Immaculada</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>2015-10-01</date><risdate>2015</risdate><volume>36</volume><issue>10</issue><spage>1103</spage><epage>1110</epage><pages>1103-1110</pages><issn>0143-3334</issn><eissn>1460-2180</eissn><abstract>Colorectal cancer (CRC) is characterized by specific patterns of copy number alterations (CNAs), which helped with the identification of driver oncogenes and tumor suppressor genes (TSGs). More recently, the usage of single nucleotide polymorphism arrays provided information of copy number neutral loss of heterozygosity, thus suggesting the occurrence of somatic uniparental disomy (UPD) and uniparental polysomy (UPP) events. The aim of this study is to establish an integrative profiling of recurrent UPDs/UPPs and CNAs in sporadic CRC. Our results indicate that regions showing high frequencies of UPD/UPP mostly coincide with regions typically involved in genomic losses. Among them, chromosome arms 3p, 5q, 9q, 10q, 14q, 17p, 17q, 20p, 21q and 22q preferentially showed UPDs/UPPs over genomic losses suggesting that tumor cells must maintain the disomic state of certain genes to favor cellular fitness. A meta-analysis using over 300 samples from The Cancer Genome Atlas confirmed our findings. Several regions affected by recurrent UPDs/UPPs contain well-known TSGs, as well as novel candidates such as ARID1A, DLC1, TCF7L2 and DMBT1. In addition, VCAN, FLT4, SFRP1 and GAS7 were also frequently involved in regions of UPD/UPP and displayed high levels of methylation. Finally, sequencing and fluorescence in situ hybridization analysis of the gene APC underlined that a somatic UPD event might represent the second hit to achieve biallelic inactivation of this TSG in colorectal tumors. In summary, our data define a profile of somatic UPDs/UPPs in sporadic CRC and highlights the importance of these events as a mechanism to achieve the inactivation of TSGs.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>26243311</pmid><doi>10.1093/carcin/bgv115</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0143-3334
ispartof Carcinogenesis (New York), 2015-10, Vol.36 (10), p.1103-1110
issn 0143-3334
1460-2180
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4598814
source Oxford Journals Online
subjects Chromosome Aberrations
Colorectal Neoplasms - complications
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Genes, Tumor Suppressor
Humans
Loss of Heterozygosity
Original Manuscript
Uniparental Disomy - genetics
Uniparental Disomy - pathology
title Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T07%3A39%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Patterns%20of%20somatic%20uniparental%20disomy%20identify%20novel%20tumor%20suppressor%20genes%20in%20colorectal%20cancer&rft.jtitle=Carcinogenesis%20(New%20York)&rft.au=Torabi,%20Keyvan&rft.date=2015-10-01&rft.volume=36&rft.issue=10&rft.spage=1103&rft.epage=1110&rft.pages=1103-1110&rft.issn=0143-3334&rft.eissn=1460-2180&rft_id=info:doi/10.1093/carcin/bgv115&rft_dat=%3Cproquest_pubme%3E1727681370%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c486t-83c0807739ed889194fe44187103427c2fcfb5c3bb99f1c684ee8033a549c08f3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1727681370&rft_id=info:pmid/26243311&rfr_iscdi=true