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SMAD4--molecular gladiator of the TGF-beta signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRAS proto-oncogene

The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the SMAD4 gene mutations with KRAS mutant status has not been explored by many studies so far. Here, in this study we aimed to inv... Full description

Journal Title: BMC cancer 17 June 2010, Vol.10, pp.300
Main Author: Sameer, A Syed
Other Authors: Chowdri, Nissar A , Syeed, Nidda , Banday, Mujeeb Z , Shah, Zaffar A , Siddiqi, Mushtaq A
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1471-2407 ; PMID: 20565773 Version:1 ; DOI: 10.1186/1471-2407-10-300
Link: http://pubmed.gov/20565773
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title: SMAD4--molecular gladiator of the TGF-beta signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRAS proto-oncogene
format: Article
creator:
  • Sameer, A Syed
  • Chowdri, Nissar A
  • Syeed, Nidda
  • Banday, Mujeeb Z
  • Shah, Zaffar A
  • Siddiqi, Mushtaq A
subjects:
  • Mutation
  • Signal Transduction
  • Adenocarcinoma -- Genetics
  • Carcinoma, Squamous Cell -- Genetics
  • Colorectal Neoplasms -- Genetics
  • Proto-Oncogene Proteins -- Genetics
  • Smad4 Protein -- Genetics
  • Transforming Growth Factor Beta -- Metabolism
  • Ras Proteins -- Genetics
ispartof: BMC cancer, 17 June 2010, Vol.10, pp.300
description: The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the SMAD4 gene mutations with KRAS mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of SMAD4 gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and KRAS mutant genotype. We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of SMAD4 and exon 1 of KRAS by PCR-SSCP and/or PCR-Direct sequencing. The overall mutation rate of mutation cluster region (MCR) region of SMAD4 gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the SMAD4 gene mutants were found to have mutations in KRAS gene as well. The association between the KRAS mutant genotype with SMAD4 mutants was found to be significant (P = or < 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the SMAD4 gene (P = or < 0.05). Our study suggests that SMAD4 gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the KRAS mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.
language: eng
source:
identifier: E-ISSN: 1471-2407 ; PMID: 20565773 Version:1 ; DOI: 10.1186/1471-2407-10-300
fulltext: fulltext
issn:
  • 14712407
  • 1471-2407
url: Link


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titleSMAD4--molecular gladiator of the TGF-beta signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRAS proto-oncogene
creatorSameer, A Syed ; Chowdri, Nissar A ; Syeed, Nidda ; Banday, Mujeeb Z ; Shah, Zaffar A ; Siddiqi, Mushtaq A
ispartofBMC cancer, 17 June 2010, Vol.10, pp.300
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subjectMutation ; Signal Transduction ; Adenocarcinoma -- Genetics ; Carcinoma, Squamous Cell -- Genetics ; Colorectal Neoplasms -- Genetics ; Proto-Oncogene Proteins -- Genetics ; Smad4 Protein -- Genetics ; Transforming Growth Factor Beta -- Metabolism ; Ras Proteins -- Genetics
descriptionThe development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the SMAD4 gene mutations with KRAS mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of SMAD4 gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and KRAS mutant genotype. We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of SMAD4 and exon 1 of KRAS by PCR-SSCP and/or PCR-Direct sequencing. The overall mutation rate of mutation cluster region (MCR) region of SMAD4 gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the SMAD4 gene mutants were found to have mutations in KRAS gene as well. The association between the KRAS mutant genotype with SMAD4 mutants was found to be significant (P = or < 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the SMAD4 gene (P = or < 0.05). Our study suggests that SMAD4 gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the KRAS mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.
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titleSMAD4--molecular gladiator of the TGF-beta signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRAS proto-oncogene
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0The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the SMAD4 gene mutations with KRAS mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of SMAD4 gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and KRAS mutant genotype.
1We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of SMAD4 and exon 1 of KRAS by PCR-SSCP and/or PCR-Direct sequencing.
2The overall mutation rate of mutation cluster region (MCR) region of SMAD4 gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the SMAD4 gene mutants were found to have mutations in KRAS gene as well. The association between the KRAS mutant genotype with SMAD4 mutants was found to be significant (P = or < 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the SMAD4 gene (P = or < 0.05).
3Our study suggests that SMAD4 gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the KRAS mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.
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abstractThe development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the SMAD4 gene mutations with KRAS mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of SMAD4 gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and KRAS mutant genotype.
doi10.1186/1471-2407-10-300
pmid20565773
issue1
date2010-06-17