scholarly journals Alterations of the base excision repair gene MUTYH in sporadic colorectal cancer

2012 ◽  
Vol 28 (2) ◽  
pp. 473-480 ◽  
Author(s):  
TAKASHI KUNO ◽  
NAGAHIDE MATSUBARA ◽  
SATOSHI TSUDA ◽  
MASAYOSHI KOBAYASHI ◽  
MIE HAMANAKA ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Sporadic Colorectal Cancer ◽  
Repair Gene ◽  
Base Excision

Prognostic impact of changes in base excision repair machinery in sporadic colorectal cancer

2018 ◽  
Vol 214 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Daniel B. Azambuja ◽  
Natalia M. Leguisamo ◽  
Helena C. Gloria ◽  
Antonio Nocchi Kalil ◽  
Ernani Rhoden ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Sporadic Colorectal Cancer ◽  
Prognostic Impact ◽  
Base Excision

scholarly journals Germline Susceptibility to Colorectal Cancer Due to Base-Excision Repair Gene Defects

2005 ◽  
Vol 77 (1) ◽  
pp. 112-119 ◽  
Author(s):  
Susan M. Farrington ◽  
Albert Tenesa ◽  
Rebecca Barnetson ◽  
Alice Wiltshire ◽  
James Prendergast ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Repair Gene ◽  
Gene Defects ◽  
Base Excision

scholarly journals Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients

2020 ◽  
Vol 21 (7) ◽  
pp. 2473 ◽  
Author(s):  
Pavel Vodicka ◽  
Marketa Urbanova ◽  
Pavol Makovicky ◽  
Kristyna Tomasova ◽  
Michal Kroupa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Base Excision Repair ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Sporadic Colorectal Cancer ◽  
Base Excision ◽  
Colorectal Cancer Patients

Oxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is proven by hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome), where germline mutations cause loss-of-function in glycosylases of base excision repair, thus enabling the accumulation of oxidative DNA damage and leading to the adenoma-colorectal cancer transition. Unrepaired oxidative DNA damage often results in G:C>T:A mutations in tumor suppressor genes and proto-oncogenes and widespread occurrence of chromosomal copy-neutral loss of heterozygosity. However, the situation is more complicated in complex and heterogeneous disease, such as sporadic colorectal cancer. Here we summarized our current knowledge of the role of oxidative DNA damage and its repair on the onset, prognosis and treatment of sporadic colorectal cancer. Molecular and histological tumor heterogeneity was considered. Our study has also suggested an additional important source of oxidative DNA damage due to intestinal dysbiosis. The roles of base excision repair glycosylases (hOGG1, MUTYH) in tumor and adjacent mucosa tissues of colorectal cancer patients, particularly in the interplay with other factors (especially microenvironment), deserve further attention. Base excision repair characteristics determined in colorectal cancer tissues reflect, rather, a disease prognosis. Finally, we discuss the role of DNA repair in the treatment of colon cancer, since acquired or inherited defects in DNA repair pathways can be effectively used in therapy.

A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer

2015 ◽  
Vol 47 (6) ◽  
pp. 668-671 ◽  
Author(s):  
Robbert D A Weren ◽  
Marjolijn J L Ligtenberg ◽  
C Marleen Kets ◽  
Richarda M de Voer ◽  
Eugène T P Verwiel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Homozygous Mutation ◽  
Adenomatous Polyposis ◽  
Repair Gene ◽  
Base Excision

Association of genetic polymorphism of the DNA base excision repair gene (APE-1 Asp/148 Glu) and HPV type (16/18) with the risk of cervix cancer in north Indian population

2008 ◽  
Vol 4 (2) ◽  
pp. 63-71 ◽  
Author(s):  
Mohammad Shekari ◽  
Ranbir Chander Sobti ◽  
Dor Mohammad Kordi Tamandani ◽  
Keyanoosh Malekzadeh ◽  
Pushpinder Kaur ◽  
...  
Keyword(s):  
Genetic Polymorphism ◽  
Base Excision Repair ◽  
Indian Population ◽  
Excision Repair ◽  
Cervix Cancer ◽  
North Indian Population ◽  
Repair Gene ◽  
Dna Base Excision Repair ◽  
Dna Base ◽  
Base Excision

scholarly journals Evaluating the utility of tumour mutational signatures for identifying hereditary colorectal cancer and polyposis syndrome carriers

Gut ◽  
2021 ◽  
pp. gutjnl-2019-320462
Author(s):  
Peter Georgeson ◽  
Bernard J Pope ◽  
Christophe Rosty ◽  
Mark Clendenning ◽  
Khalid Mahmood ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Excision Repair ◽  
Area Under The Curve ◽  
Hereditary Colorectal Cancer ◽  
Base Substitution ◽  
Mutational Signatures ◽  
Repair Gene ◽  
Dna Mismatch ◽  
Pathogenic Variants ◽  
Base Excision

ObjectiveGermline pathogenic variants (PVs) in the DNA mismatch repair (MMR) genes and in the base excision repair gene MUTYH underlie hereditary colorectal cancer (CRC) and polyposis syndromes. We evaluated the robustness and discriminatory potential of tumour mutational signatures in CRCs for identifying germline PV carriers.DesignWhole-exome sequencing of formalin-fixed paraffin-embedded (FFPE) CRC tissue was performed on 33 MMR germline PV carriers, 12 biallelic MUTYH germline PV carriers, 25 sporadic MLH1 methylated MMR-deficient CRCs (MMRd controls) and 160 sporadic MMR-proficient CRCs (MMRp controls) and included 498 TCGA CRC tumours. COSMIC V3 single base substitution (SBS) and indel (ID) mutational signatures were assessed for their ability to differentiate CRCs that developed in carriers from non-carriers.ResultsThe combination of mutational signatures SBS18 and SBS36 contributing >30% of a CRC’s signature profile was able to discriminate biallelic MUTYH carriers from all other non-carrier control CRCs with 100% accuracy (area under the curve (AUC) 1.0). SBS18 and SBS36 were associated with specific MUTYH variants p.Gly396Asp (p=0.025) and p.Tyr179Cys (p=5×10-5), respectively. The combination of ID2 and ID7 could discriminate the 33 MMR PV carrier CRCs from the MMRp control CRCs (AUC 0.99); however, SBS and ID signatures, alone or in combination, could not provide complete discrimination (AUC 0.79) between CRCs from MMR PV carriers and sporadic MMRd controls.ConclusionAssessment of SBS and ID signatures can discriminate CRCs from biallelic MUTYH carriers and MMR PV carriers from non-carriers with high accuracy, demonstrating utility as a potential diagnostic and variant classification tool.

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