Journal ArticleDOI
Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3′ exons of TACSTD1
Marjolijn J L Ligtenberg,Roland P. Kuiper,Tsun Leung Chan,Tsun Leung Chan,Monique Goossens,Konnie M. Hebeda,Marsha Voorendt,Tracy Y H Lee,Danielle Bodmer,Eveline Hoenselaar,Sandra J B Hendriks-Cornelissen,Wai Yin Tsui,Chi Kwan Kong,Han G. Brunner,Ad Geurts van Kessel,Siu Tsan Yuen,Siu Tsan Yuen,J. Han van Krieken,Suet Yi Leung,Suet Yi Leung,Nicoline Hoogerbrugge +20 more
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TLDR
Patients from Dutch and Chinese families with MSH2-deficient tumors carrying heterozygous germline deletions of the last exons of TACSTD1, a gene directly upstream of MSH1 encoding Ep-CAM, are described, revealing a correlation between activity of the mutated TAC STD1 allele and epigenetic inactivation of the corresponding MSH 2 allele.Abstract:
Lynch syndrome patients are susceptible to colorectal and endometrial cancers owing to inactivating germline mutations in mismatch repair genes, including MSH2 (ref. 1). Here we describe patients from Dutch and Chinese families with MSH2-deficient tumors carrying heterozygous germline deletions of the last exons of TACSTD1, a gene directly upstream of MSH2 encoding Ep-CAM. Due to these deletions, transcription of TACSTD1 extends into MSH2. The MSH2 promoter in cis with the deletion is methylated in Ep-CAM positive but not in Ep-CAM negative normal tissues, thus revealing a correlation between activity of the mutated TACSTD1 allele and epigenetic inactivation of the corresponding MSH2 allele. Gene silencing by transcriptional read-through of a neighboring gene in either sense, as demonstrated here, or antisense direction, could represent a general mutational mechanism. Depending on the expression pattern of the neighboring gene that lacks its normal polyadenylation signal, this may cause either generalized or mosaic patterns of epigenetic inactivation.read more
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Journal ArticleDOI
A decade of exploring the cancer epigenome — biological and translational implications
Stephen B. Baylin,Peter A. Jones +1 more
TL;DR: Next-generation sequencing is providing a window for visualizing the human epigenome and how it is altered in cancer, including linking epigenetic abnormalities to mutations in genes that control DNA methylation, the packaging and the function of DNA in chromatin, and metabolism.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines
TL;DR: Lymphedema is a common complication after treatment for breast cancer and factors associated with increased risk of lymphedEMA include extent of axillary surgery, axillary radiation, infection, and patient obesity.
Journal ArticleDOI
Microsatellite Instability in Colorectal Cancer
C. Richard Boland,Ajay Goel +1 more
TL;DR: Colorectal tumors with MSI have distinctive features, including a tendency to arise in the proximal colon, lymphocytic infiltrate, and a poorly differentiated, mucinous or signet ring appearance, and do not have the same response to chemotherapeutics.
Journal ArticleDOI
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.
Sapna Syngal,Randall E. Brand,James M. Church,Francis M. Giardiello,Heather Hampel,Randall W. Burt +5 more
TL;DR: Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers.
Journal ArticleDOI
Hereditary and Familial Colon Cancer
TL;DR: This review examines the colon cancer syndromes, their genetics and management, and also the common familial colon cancers with current genetic advances and screening guidelines.
References
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Book ChapterDOI
de la Chapelle, A.
Peter Beighton,Greta Beighton +1 more
TL;DR: De la Chapelle dysplasia, also known as atelosteogenesis type II, is a lethal form of neonatal dwarfism in which gross limb shortening is associated with a characteristic triangular configuration of the radius and ulna.
Journal ArticleDOI
Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma
James G. Herman,Asad Umar,Kornelia Polyak,Jeremy R. Graff,Nita Ahuja,Jean Pierre J. Issa,Sanford Markowitz,Sanford Markowitz,James K V Willson,Stanley R. Hamilton,Kenneth W. Kinzler,Michael F. Kane,Richard D. Kolodner,Bert Vogelstein,Thomas A. Kunkel,Stephen B. Baylin +15 more
TL;DR: The results suggest that microsatellite instability in sporadic colorectal cancer often results from epigenetic inactivation of hMLH1 in association with DNA methylation.
Journal ArticleDOI
Hereditary Colorectal Cancer
TL;DR: This article provides an in-depth review of the two most common forms of familial colorectal cancer, and the identification of those at risk and the use of appropriate colonoscopic screening.
Journal Article
Methylation of the hMLH1 Promoter Correlates with Lack of Expression of hMLH1 in Sporadic Colon Tumors and Mismatch Repair-defective Human Tumor Cell Lines
Michael F. Kane,Massimo Loda,Gretchen M. Gaida,Lipman J,Rajesh Mishra,Harvey Goldman,J. M. Jessup,Richard D. Kolodner +7 more
TL;DR: Analysis of sporadic colorectal tumors for the expression of hMLH1 by immunohistochemistry indicates that DNA methylation is likely to be a common mode of mismatch repair gene inactivation in sporadic tumors.
Journal ArticleDOI
Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA
Wenqiang Yu,David Gius,Patrick Onyango,Kristi Muldoon-Jacobs,Judith E. Karp,Andrew P. Feinberg,Hengmi Cui +6 more
TL;DR: It is shown that many TSGs have nearby antisense RNAs, and an inverse relation between p15 antisense (p15AS) and p15 sense expression in leukaemia is found, which suggests natural antisense RNA may be a trigger for heterochromatin formation and DNA methylation in TSG silencing in tumorigenesis.
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