scholarly journals Risk of extracolonic cancers for people with biallelic and monoallelic mutations inMUTYH

2016 ◽  
Vol 139 (7) ◽  
pp. 1557-1563 ◽  
Author(s):  
Aung Ko Win ◽  
Jeanette C. Reece ◽  
James G. Dowty ◽  
Daniel D. Buchanan ◽  
Mark Clendenning ◽  
...  
Keyword(s):  
Extracolonic Cancers

Colorectal and Extracolonic Cancers Detected at Screening CT Colonography in 10 286 Asymptomatic Adults

Radiology ◽  
2010 ◽  
Vol 255 (1) ◽  
pp. 83-88 ◽  
Author(s):  
Perry J. Pickhardt ◽  
David H. Kim ◽  
Ryan J. Meiners ◽  
Kimberly S. Wyatt ◽  
Meghan E. Hanson ◽  
...  
Keyword(s):  
Ct Colonography ◽  
Extracolonic Cancers

1054 Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH

2015 ◽  
Vol 51 ◽  
pp. S163
Author(s):  
A. Win ◽  
J. Reece ◽  
J. Dowty ◽  
D. Buchanan ◽  
M. Clendenning ◽  
...  
Keyword(s):  
Extracolonic Cancers

scholarly journals Risks of Primary Extracolonic Cancers Following Colorectal Cancer in Lynch Syndrome

2012 ◽  
Vol 104 (18) ◽  
pp. 1363-1372 ◽  
Author(s):  
A. K. Win ◽  
N. M. Lindor ◽  
J. P. Young ◽  
F. A. Macrae ◽  
G. P. Young ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Extracolonic Cancers

scholarly journals The majority of β-catenin mutations in colorectal cancer is homozygous

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Alexander Arnold ◽  
Moritz Tronser ◽  
Christine Sers ◽  
Aysel Ahadova ◽  
Volker Endris ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Animal Studies ◽  
Mutational Status ◽  
Mutational Hotspots ◽  
A Cell ◽  
Cytoplasmic Accumulation ◽  
Selection Of ◽  
Extracolonic Cancers ◽  
E Cadherin

Abstract Background β-catenin activation plays a crucial role for tumourigenesis in the large intestine but except for Lynch syndrome (LS) associated cancers stabilizing mutations of β-catenin gene (CTNNB1) are rare in colorectal cancer (CRC). Previous animal studies provide an explanation for this observation. They showed that CTNNB1 mutations induced transformation in the colon only when CTNNB1 was homozygously mutated or when membranous β-catenin binding was hampered by E-cadherin haploinsufficiency. We were interested, if these mechanisms are also found in human CTNNB1 mutated CRCs. Results Among 869 CRCs stabilizing CTNNB1 mutations were found in 27 cases. Homo- or hemizygous CTNNB1 mutations were detected in 74% of CTNNB1 mutated CRCs (13 microsatellite instabile (MSI-H), 7 microsatellite stabile (MSS)) but only in 3% (1/33) of extracolonic CTNNB1 mutated cancers. In contrast to MSS CRC, CTNNB1 mutations at codon 41 or 45 were highly selected in MSI-H CRC. Of the examined three CRC cell lines, β-catenin and E-cadherin expression was similar in cell lines without or with hetereozygous CTNNB1 mutations (DLD1 and HCT116), while a reduced E-cadherin expression combined with cytoplasmic accumulation of β-catenin was found in a cell line with homozygous CTNNB1 mutation (LS180). Reduced expression of E-cadherin in human MSI-H CRC tissue was identified in 60% of investigated cancers, but no association with the CTNNB1 mutational status was found. Conclusions In conclusion, this study shows that in contrast to extracolonic cancers stabilizing CTNNB1 mutations in CRC are commonly homo- or hemizygous indicating a higher threshold of β-catenin stabilization to be required for transformation in the colon as compared to extracolonic sites. Moreover, we found different mutational hotspots in CTNNB1 for MSI-H and MSS CRCs suggesting a selection of different effects on β-catenin stabilization according to the molecular pathway of tumourigenesis. Reduced E-cadherin expression in CRC may further contribute to higher levels of transcriptionally active β-catenin, but it is not directly linked to the CTNNB1 mutational status.

scholarly journals Same MSH2 Gene Mutation But Variable Phenotypes in 2 Families With Lynch Syndrome: Two Case Reports and Review of Genotype-Phenotype Correlation

2018 ◽  
Vol 11 ◽  
pp. 117954761775394 ◽  
Author(s):  
Raffaella Liccardo ◽  
Marina De Rosa ◽  
Francesca Duraturo
Keyword(s):  
Lynch Syndrome ◽  
Autosomal Dominant ◽  
Colonic Cancer ◽  
Case Reports ◽  
Phenotypic Expression ◽  
Point Mutations ◽  
Phenotype Correlation ◽  
Dna Mismatch ◽  
Large Rearrangements ◽  
Extracolonic Cancers

Lynch syndrome is an autosomal dominant syndrome that can be subdivided into Lynch syndrome I, or site-specific colonic cancer, and Lynch syndrome II, or extracolonic cancers, particularly carcinomas of the stomach, endometrium, biliary and pancreatic systems, and urinary tract. Lynch syndrome is associated with point mutations and large rearrangements in DNA MisMatch Repair ( MMR) genes. This syndrome shows a variable phenotypic expression in people who carry pathogenetic mutations. So far, a correlation in genotype-phenotype has not been definitely established. In this study, we describe 2 Lynch syndrome cases presenting with the same genotype but different phenotypes and discuss possible reasons for this.

scholarly journals Clean Colorectum at Diagnostic Colonoscopy: Subsequent Detection of Extracolonic Malignancies by Plasma Protein Biomarkers?

2018 ◽  
Vol 10 ◽  
pp. 1179299X1877697 ◽  
Author(s):  
Michael Wilhelmsen ◽  
Ib J Christensen ◽  
Lars N Jørgensen ◽  
Mogens R Madsen ◽  
Jesper Vilandt ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Specific Antigen ◽  
Protein Biomarkers ◽  
Diagnostic Colonoscopy ◽  
Lung Cancers ◽  
Extracolonic Cancer ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk ◽  
Age And Sex ◽  
Extracolonic Cancers

Introduction: Most of the subjects undergoing diagnostic colonoscopy do not have neoplastic bowel lesions. Potentially, some of the symptoms may therefore be caused by extracolonic malignancy, and subjects with persisting symptoms may need subsequent examinations. Blood-based, cancer-associated biomarkers may aid in directing the examinations for other specific malignant diseases. Methods: EDTA plasma samples available from a previous prospective study of subjects undergoing diagnostic colonoscopy were used for analysis of 18 protein biomarkers. The study population of 3732 subjects included 400 patients with colorectal cancer (CRC) and 177 patients with extracolonic malignancies. Univariable analysis of the association of specific biomarkers and extracolonic cancers included those with 10 or more cases. Subsequently, reduced models of 4 or 6 biomarkers, respectively, were established by choosing those with the highest likelihood; age and sex were included as well. Results: Univariable analyses showed that CyFra21-1 had an area under curve (AUC) of 0.87 for lung cancers (n = 33), CA19-9 had an AUC of 0.85 for pancreatic cancer (n = 22), CA125 had an AUC of 0.95 for ovary cancer (n = 16), B2M had an AUC of 0.81 for non-Hodgkin lymphoma (n = 12), and total prostate-specific antigen had an AUC of 0.99 for prostate cancer (n = 10). The multivariable analysis of 4 or 6 biomarkers plus age and sex as explanatory variables showed AUCs of 0.82 to 0.85 both for extracolonic cancers and CRC. The 4 biomarkers included in the model for detection of extracolonic cancers were CA125, hsCRP, CA19-9, and CyFra21-1; the 2 additional for the 6 biomarkers model were CEA and Galectin-3. Similarly, the 4 biomarkers included in the model for detection of CRC were CEA, CyFra21-1, Ferritin, and HE4; the two additional for the 6 biomarkers model were hsCRP and Pepsinogen 2. Conclusions: Results of this study indicate that it may be possible to detect subjects that have an increased risk of extracolonic cancer following a colonoscopy without findings of neoplastic lesions. Combinations of various protein biomarkers may direct subsequent examination after colonoscopy with clean colorectum. The results, although preliminary, may form the basis for additional research directed both for primary examinations of subjects with symptoms of malignancy and subsequent examinations after colonoscopy.

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