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Kras Gene Mutation and RASSF1A, FHIT and MGMT Gene Promoter Hypermethylation: Indicators of Tumor Staging and Metastasis in Adenocarcinomatous Sporadic Colorectal Cancer in Indian Population. e60142
Objective Colorectal cancer (CRC) development involves underlying modifications at genetic/epigenetic level. This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with...
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Published in: | PloS one 2013-04, Vol.8 (4) |
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creator | Sinha, Rupal Hussain, Showket Mehrotra, Ravi Kumar, R Suresh Kumar, Kapil Pande, Pankaj Doval, Dinesh Chandra Basir, Seemi Farhat Bharadwaj, Mausumi |
description | Objective Colorectal cancer (CRC) development involves underlying modifications at genetic/epigenetic level. This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with clinicopathological variables of the disease. Methods One hundred and twenty four consecutive surgically resected tissues (62 tumor and equal number of normal adjacent controls) of primary sporadic CRC were included and patient details including demographic characteristics, lifestyle/food or drinking habits, clinical and histopathological profiles were recorded. Polymerase chain reaction - Restriction fragment length polymorphism and direct sequencing for Kras gene mutation and Methylation Specific-PCR for RASSF1A, FHIT and MGMT genes was performed. Results Kras gene mutation at codon 12 & 13 and methylated RASSF1A, FHIT and MGMT gene was observed in 47%, 19%, 47%, 37% and 47% cases, respectively. Alcohol intake and smoking were significantly associated with presence of Kras mutation (codon 12) and MGMT methylation (p-value |
doi_str_mv | 10.1371/journal.pone.0060142 |
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This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with clinicopathological variables of the disease. Methods One hundred and twenty four consecutive surgically resected tissues (62 tumor and equal number of normal adjacent controls) of primary sporadic CRC were included and patient details including demographic characteristics, lifestyle/food or drinking habits, clinical and histopathological profiles were recorded. Polymerase chain reaction - Restriction fragment length polymorphism and direct sequencing for Kras gene mutation and Methylation Specific-PCR for RASSF1A, FHIT and MGMT genes was performed. Results Kras gene mutation at codon 12 & 13 and methylated RASSF1A, FHIT and MGMT gene was observed in 47%, 19%, 47%, 37% and 47% cases, respectively. Alcohol intake and smoking were significantly associated with presence of Kras mutation (codon 12) and MGMT methylation (p-value <0.049). Tumor stage and metastasis correlated with presence of mutant Kras codon 12 (p-values 0.018, 0.044) and methylated RASSF1A (p-values 0.034, 0.044), FHIT (p-values 0.001, 0.047) and MGMT (p-values 0.018, 0.044) genes. Combinatorial effect of gene mutation/methylation was also observed (p-value <0.025). Overall, tumor stage 3, moderately differentiated tumors, presence of lymphatic invasion and absence of metastasis was more frequently observed in tumors with mutated Kras and/or methylated RASSF1A, FHIT and MGMT genes. Conclusion Synergistic interrelationship between these genes in sporadic CRC may be used as diagnostic/prognostic markers in assessing the overall pathological status of CRC.</description><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0060142</identifier><language>eng</language><subject>Alcoholic beverages</subject><ispartof>PloS one, 2013-04, Vol.8 (4)</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902,36990</link.rule.ids></links><search><creatorcontrib>Sinha, Rupal</creatorcontrib><creatorcontrib>Hussain, Showket</creatorcontrib><creatorcontrib>Mehrotra, Ravi</creatorcontrib><creatorcontrib>Kumar, R Suresh</creatorcontrib><creatorcontrib>Kumar, Kapil</creatorcontrib><creatorcontrib>Pande, Pankaj</creatorcontrib><creatorcontrib>Doval, Dinesh Chandra</creatorcontrib><creatorcontrib>Basir, Seemi Farhat</creatorcontrib><creatorcontrib>Bharadwaj, Mausumi</creatorcontrib><title>Kras Gene Mutation and RASSF1A, FHIT and MGMT Gene Promoter Hypermethylation: Indicators of Tumor Staging and Metastasis in Adenocarcinomatous Sporadic Colorectal Cancer in Indian Population. e60142</title><title>PloS one</title><description>Objective Colorectal cancer (CRC) development involves underlying modifications at genetic/epigenetic level. This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with clinicopathological variables of the disease. Methods One hundred and twenty four consecutive surgically resected tissues (62 tumor and equal number of normal adjacent controls) of primary sporadic CRC were included and patient details including demographic characteristics, lifestyle/food or drinking habits, clinical and histopathological profiles were recorded. Polymerase chain reaction - Restriction fragment length polymorphism and direct sequencing for Kras gene mutation and Methylation Specific-PCR for RASSF1A, FHIT and MGMT genes was performed. Results Kras gene mutation at codon 12 & 13 and methylated RASSF1A, FHIT and MGMT gene was observed in 47%, 19%, 47%, 37% and 47% cases, respectively. Alcohol intake and smoking were significantly associated with presence of Kras mutation (codon 12) and MGMT methylation (p-value <0.049). Tumor stage and metastasis correlated with presence of mutant Kras codon 12 (p-values 0.018, 0.044) and methylated RASSF1A (p-values 0.034, 0.044), FHIT (p-values 0.001, 0.047) and MGMT (p-values 0.018, 0.044) genes. Combinatorial effect of gene mutation/methylation was also observed (p-value <0.025). Overall, tumor stage 3, moderately differentiated tumors, presence of lymphatic invasion and absence of metastasis was more frequently observed in tumors with mutated Kras and/or methylated RASSF1A, FHIT and MGMT genes. Conclusion Synergistic interrelationship between these genes in sporadic CRC may be used as diagnostic/prognostic markers in assessing the overall pathological status of CRC.</description><subject>Alcoholic beverages</subject><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqVj89Kw0AQhxdBsP55Aw9z9GDjblJT660U2xQpFJN7GdJp3bKZibubQ1_Q5zK2voAwMDD8vt_HKHVvdGKysXk6SOcZXdIKU6J1rs0ovVADM8nSYZ7q7Epdh3DQ-jl7yfOB-n73GGBBTLDqIkYrDMhb-JiW5dxMH2FeLKvTZbVYVefg2ksjkTwUx5Z8Q_Hz6E7kKyx5a2uM4gPIDqquEQ9lxL3l_bmEIoZ-bADLMN0SS42-tixNT3UBylY89h0wEyee6ogOZsh1b-uB33pkWEvbnY0J0OnDW3W5Qxfo7m_fqIf5WzUrhq2Xr45C3DQ21OQcMvWajcny8WiSTozO_hH9AWOXcxY</recordid><startdate>20130401</startdate><enddate>20130401</enddate><creator>Sinha, Rupal</creator><creator>Hussain, Showket</creator><creator>Mehrotra, Ravi</creator><creator>Kumar, R Suresh</creator><creator>Kumar, Kapil</creator><creator>Pande, Pankaj</creator><creator>Doval, Dinesh Chandra</creator><creator>Basir, Seemi Farhat</creator><creator>Bharadwaj, Mausumi</creator><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20130401</creationdate><title>Kras Gene Mutation and RASSF1A, FHIT and MGMT Gene Promoter Hypermethylation: Indicators of Tumor Staging and Metastasis in Adenocarcinomatous Sporadic Colorectal Cancer in Indian Population. e60142</title><author>Sinha, Rupal ; Hussain, Showket ; Mehrotra, Ravi ; Kumar, R Suresh ; Kumar, Kapil ; Pande, Pankaj ; Doval, Dinesh Chandra ; Basir, Seemi Farhat ; Bharadwaj, Mausumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_miscellaneous_13674929103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Alcoholic beverages</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sinha, Rupal</creatorcontrib><creatorcontrib>Hussain, Showket</creatorcontrib><creatorcontrib>Mehrotra, Ravi</creatorcontrib><creatorcontrib>Kumar, R Suresh</creatorcontrib><creatorcontrib>Kumar, Kapil</creatorcontrib><creatorcontrib>Pande, Pankaj</creatorcontrib><creatorcontrib>Doval, Dinesh Chandra</creatorcontrib><creatorcontrib>Basir, Seemi Farhat</creatorcontrib><creatorcontrib>Bharadwaj, Mausumi</creatorcontrib><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sinha, Rupal</au><au>Hussain, Showket</au><au>Mehrotra, Ravi</au><au>Kumar, R Suresh</au><au>Kumar, Kapil</au><au>Pande, Pankaj</au><au>Doval, Dinesh Chandra</au><au>Basir, Seemi Farhat</au><au>Bharadwaj, Mausumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kras Gene Mutation and RASSF1A, FHIT and MGMT Gene Promoter Hypermethylation: Indicators of Tumor Staging and Metastasis in Adenocarcinomatous Sporadic Colorectal Cancer in Indian Population. e60142</atitle><jtitle>PloS one</jtitle><date>2013-04-01</date><risdate>2013</risdate><volume>8</volume><issue>4</issue><eissn>1932-6203</eissn><abstract>Objective Colorectal cancer (CRC) development involves underlying modifications at genetic/epigenetic level. This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with clinicopathological variables of the disease. Methods One hundred and twenty four consecutive surgically resected tissues (62 tumor and equal number of normal adjacent controls) of primary sporadic CRC were included and patient details including demographic characteristics, lifestyle/food or drinking habits, clinical and histopathological profiles were recorded. Polymerase chain reaction - Restriction fragment length polymorphism and direct sequencing for Kras gene mutation and Methylation Specific-PCR for RASSF1A, FHIT and MGMT genes was performed. Results Kras gene mutation at codon 12 & 13 and methylated RASSF1A, FHIT and MGMT gene was observed in 47%, 19%, 47%, 37% and 47% cases, respectively. Alcohol intake and smoking were significantly associated with presence of Kras mutation (codon 12) and MGMT methylation (p-value <0.049). Tumor stage and metastasis correlated with presence of mutant Kras codon 12 (p-values 0.018, 0.044) and methylated RASSF1A (p-values 0.034, 0.044), FHIT (p-values 0.001, 0.047) and MGMT (p-values 0.018, 0.044) genes. Combinatorial effect of gene mutation/methylation was also observed (p-value <0.025). Overall, tumor stage 3, moderately differentiated tumors, presence of lymphatic invasion and absence of metastasis was more frequently observed in tumors with mutated Kras and/or methylated RASSF1A, FHIT and MGMT genes. Conclusion Synergistic interrelationship between these genes in sporadic CRC may be used as diagnostic/prognostic markers in assessing the overall pathological status of CRC.</abstract><doi>10.1371/journal.pone.0060142</doi></addata></record> |
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title | Kras Gene Mutation and RASSF1A, FHIT and MGMT Gene Promoter Hypermethylation: Indicators of Tumor Staging and Metastasis in Adenocarcinomatous Sporadic Colorectal Cancer in Indian Population. e60142 |
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