Update on Hereditary Colorectal Cancer

Silva, Felipe Cavalcanti Carneiro da; Wernhoff, Patrik; Dominguez-Barrera, Constantino; Dominguez‐Valentin, Mev

doi:10.21873/anticanres.10983

Cited by 58 publications

(46 citation statements)

References 59 publications

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“…We used samples from colon resections from Puerto Rican patients with no family history of colorectal cancer or inflammatory bowel disease. Family history is the main component of the Amsterdam II criteria for Identifying individuals with Hereditary Non-Polyposis Colorectal Cancer (Lynch syndrome), thus individuals with Lynch syndrome are not likely included in our study (19,20). We found that 6.3% of AD, 9.1% of HGDs and 9.4% of CAs showed loss of expression of both MLH1 and PMS2 proteins.…”

Section: Discussionmentioning

confidence: 99%

Frequency of Mismatch Repair Protein Deficiency in a Puerto Rican Population with Colonic Adenoma and Adenocarcinoma

Reverón

Lopez

Gutierrez

et al. 2018

Cancer Genomics Proteomics

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Section: Discussionmentioning

confidence: 99%

Frequency of Mismatch Repair Protein Deficiency in a Puerto Rican Population with Colonic Adenoma and Adenocarcinoma

Reverón

Lopez

Gutierrez

et al. 2018

Cancer Genomics Proteomics

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“…Lynch Syndrome (LS) is the most prevalent adult‐onset hereditary cancer syndrome (#MIM 120435). Affected patients carry heterozygous germline mutations in one of the main DNA mismatch repair (MMR) genes (ie, MLH1, MSH2, MSH6 , and PMS2) and are at an increased risk to develop—upon somatic inactivation of the second allele—multiple synchronous or metachronous colonic and extra‐colonic (eg, endometrium, ovarian, stomach, duodenum) malignancies . Tumors typically arise in the fourth or fifth decade.…”

Section: Introductionmentioning

confidence: 99%

“…This wide tumor spectrum is a consequence of the loss of MMR function in all tissues already throughout embryogenesis and results in continuous accumulation of additional genetic defects throughout development . Hence, the pathogenetic and clinical presentation of CMMR‐D is somehow different from LS, in which MMR‐D is confined to (pre)cancerous cells . Given those differences between both syndromes, there are however, some features quite common to CMMR‐D and LS.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 Hence, the pathogenetic and clinical presentation of CMMR-D is somehow different from LS, in which MMR-D is confined to (pre)cancerous cells. 2,4 Given those differences between both syndromes, there are however, some features quite common to CMMR-D and LS. Loss of a functional MMR system is the driver for carcinogenesis and is closely linked to hypermutation-a finding not particularly surprising.…”

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confidence: 99%

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Frameshift mutational target gene analysis identifies similarities and differences in constitutional mismatch repair‐deficiency and Lynch syndrome

Maletzki

Huehns

Bauer

et al. 2017

Molecular Carcinogenesis

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Mismatch-repair deficient (MMR-D) malignancies include Lynch Syndrome (LS), which is secondary to germline mutations in one of the MMR genes, and the rare childhood-form of constitutional mismatch repair-deficiency (CMMR-D); caused by bi-allelic MMR gene mutations. A hallmark of LS-associated cancers is microsatellite instability (MSI), characterized by coding frameshift mutations (cFSM) in target genes. By contrast, tumors arising in CMMR-D patients are thought to display a somatic mutation pattern differing from LS. This study has the main goal to identify cFSM in MSI target genes relevant in CMMR-D and to compare the spectrum of common somatic mutations, including alterations in DNA polymerases POLE and D1 between LS and CMMR-D. CMMR-D-associated tumors harbored more somatic mutations compared to LS cases, especially in the TP53 gene and in POLE and POLD1, where novel mutations were additionally identified. Strikingly, MSI in classical mononucleotide markers BAT40 and CAT25 was frequent in CMMR-D cases. MSI-target gene analysis revealed mutations in CMMR-D-associated tumors, some of them known to be frequently hit in LS, such as RNaseT2, HT001, and TGFβR2. Our results imply a general role for these cFSM as potential new drivers of MMR-D tumorigenesis.

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“…A defect in the human MMR genes MSH2 and MLH1 causes microsatellite instability and a predisposition to colon and other types of cancer (Lynch et al 2009; Da Silva et al 2016). Mutations in other MMR genes are rarely correlated with cancer, probably due to functional redundancy.…”

mentioning

confidence: 99%

Schizosaccharomyces pombeMutSα and MutLα Maintain Stability of Tetra-Nucleotide Repeats and Msh3 of Hepta-Nucleotide Repeats

Villahermosa

Christensen

Knapp

et al. 2017

G3 Genes|Genomes|Genetics

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Defective mismatch repair (MMR) in humans is associated with colon cancer and instability of microsatellites, that is, DNA sequences with one or several nucleotides repeated. Key factors of eukaryotic MMR are the heterodimers MutSa (Msh2-Msh6), which recognizes base-base mismatches and unpaired nucleotides in DNA, and MutLa (Mlh1-Pms1), which facilitates downstream steps. In addition, MutSb (Msh2-Msh3) recognizes DNA loops of various sizes, although our previous data and the data presented here suggest that Msh3 of Schizosaccharomyces pombe does not play a role in MMR. To test microsatellite stability in S. pombe and hence DNA loop repair, we have inserted tetra-, penta-, and hepta-nucleotide repeats in the ade6 gene and determined their Ade + reversion rates and spectra in wild type and various mutants. Our data indicate that loops with four unpaired nucleotides in the nascent and the template strand are the upper limit of MutSa-and MutLa-mediated MMR in S. pombe. Stability of hepta-nucleotide repeats requires Msh3 and Exo1 in MMR-independent processes as well as the DNA repair proteins Rad50, Rad51, and Rad2 FEN1 . Most strikingly, mutation rates in the double mutants msh3 exo1 and msh3 rad51 were decreased when compared to respective single mutants, indicating that Msh3 prevents error prone processes carried out by Exo1 and Rad51. We conclude that Msh3 has no obvious function in MMR in S. pombe, but contributes to DNA repeat stability in MMR-independent processes.

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Update on Hereditary Colorectal Cancer

Cited by 58 publications

References 59 publications

Frequency of Mismatch Repair Protein Deficiency in a Puerto Rican Population with Colonic Adenoma and Adenocarcinoma

Frequency of Mismatch Repair Protein Deficiency in a Puerto Rican Population with Colonic Adenoma and Adenocarcinoma

Frameshift mutational target gene analysis identifies similarities and differences in constitutional mismatch repair‐deficiency and Lynch syndrome

Schizosaccharomyces pombeMutSα and MutLα Maintain Stability of Tetra-Nucleotide Repeats and Msh3 of Hepta-Nucleotide Repeats

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