Multiple epithelial and nonepithelial tumors in hereditary nonpolyposis colorectal cancer: characterization of germline and somatic mutations of the MSH2 gene and heterogeneity of replication error phenotypes

Huang, Rui; Chao, Chung-Faye; Ding, Dah‐Ching; Yu, Cheng; Chang, Cheng‐Chang; Lai, Hung Chen; Mu, Yu; Liu, Hang Seng; Chu, T. Ming

doi:10.1016/j.cancergencyto.2004.01.003

Cited by 14 publications

(10 citation statements)

References 28 publications

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“…Hereditary non-polyposis colorectal cancer (HNPCC) is a highly penetrant, autosomal dominant disorder characterized by the early onset of colorectal cancer (CRC) and endometrial cancer (EC) (Dovrat et al, 2005;Huang et al, 2004;Hegde et al, 2005). HNPCC is often associated with inherited mutations of mismatch repair (MMR) genes (Hendriks et al, 2004), which consists of at least 9 genes, hMSH2, hMSH3,hMSH5,hMSH6,hMSH8,hMLH1,hMLH3,hPMS1, and hPMS2 (http://www.ncbi.nlm.nih.gov/sites/entrez).…”

Section: Meta-analysis Of Msh6 Gene Mutation Frequency In Colorectal mentioning

confidence: 99%

Meta-Analysis ofMSH6Gene Mutation Frequency in Colorectal and Endometrial Cancers

Zhao

Wang

et al. 2009

Journal of Toxicology and Environmental Health, Part A

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Studies on mutations and mutation frequencies of the MSH6 gene, which mainly focus on new types of mutations in small samples, have been published ever since the first report of MSH6 mutation in two atypical hereditary non-polyposis colorectal cancer patients. However, the results remain inconsistent. Therefore, a systematic review was conducted and a meta-analysis was undertaken to determine the frequency of MSH6 mutation in colorectal and endometrial cancers. From 27 studies, 180 cases with MSH6 mutation in a total of 3196 cases were detected. In colorectal and endometrial cancers the MSH6 mutation frequency is 7.2 and 9.6%, respectively. MSH6 mutation frequency was 10.4% in hereditary non-polyposis colorectal cancer patients, 7.1% in atypical hereditary non-polyposis colorectal cancer patients, and 5.9% in sporadic patients. The frequency of MSH6 mutation in high microsatellite instability (MSI-H) was 11.6% and in low microsatellite instability (MSI-L) cases was (13.3%), which were higher than in microsatellite stability (MSS) cases (1.7%). The mean age of the earliest onset of colorectal and endometrial cancers in MSH6 mutation carriers was 51.2 and 56.5 yr, respectively. Data suggest that the frequency of MSH6 mutation is higher in hereditary non-polyposis colorectal cancer patients than in atypical hereditary non-polyposis colorectal cancer and sporadic patients. MSH6 mutation frequency was also higher in endometrial than colorectal cancers. The mean age of earliest onset of endometrial cancer (56.5 yr) is older than for colorectal cancer (51.2 yr) in carriers of MSH6 mutation. Our results provide evidence for clinical genetic testing and counseling.

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Section: Meta-analysis Of Msh6 Gene Mutation Frequency In Colorectal mentioning

confidence: 99%

Meta-Analysis ofMSH6Gene Mutation Frequency in Colorectal and Endometrial Cancers

Zhao

Wang

et al. 2009

Journal of Toxicology and Environmental Health, Part A

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“…These cancers include adrenocortical adenocarcinoma [9-11], thyroid carcinoma [10], peritoneal mesothelioma [11], malignant fibrohistiocytoma [12,13], rhabdomyosarcoma [14], dermatofibrosarcoma [15], leiomyosarcoma [16-19], liposarcoma [19], carcinoid tumour [20], non-Hodgkin lymphoma [21], malignant melanoma [22], pancreas [11,23], prostate [24] and breast cancers [25-39]. However, for these tumors except pancreatic cancer [40], an increase in risk for MMR gene mutation carriers compared with the population (or non-carriers) has not been observed.…”

Section: Introductionmentioning

confidence: 99%

Risk of breast cancer in Lynch syndrome: a systematic review

2013

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IntroductionLynch syndrome is an autosomal dominantly inherited disorder of cancer susceptibility caused by germline mutations in the DNA mismatch repair (MMR) genes. Mutation carriers have a substantial burden of increased risks of cancers of the colon, rectum, endometrium and several other organs which generally occur at younger ages than for the general population. The issue of whether breast cancer risk is increased for MMR gene mutation carriers has been debated with evidence for and against this association.MethodsUsing the PUBMED, we identified all relevant studies of breast cancer associated with Lynch syndrome that were published by 15 December 2012. In the review, we included: (i) molecular studies that reported microsatellite instability and/or immunohistochemistry in breast cancer tumors of MMR gene mutation carriers; and (ii) risk studies that investigated risk of breast cancer for confirmed MMR gene mutation carriers or families or clinically and/or pathologically defined Lynch syndrome families.ResultsWe identified 15 molecular studies and, when combined, observed 62 of 122 (51%; 95% CI 42 to 60%) breast cancers in MMR gene mutation carriers were MMR-deficient. Of the 21 risk studies identified, 13 did not observe statistical evidence for an association of breast cancer risk with Lynch syndrome while 8 studies found an increased risk of breast cancer ranging from 2- to 18-fold compared with the general population (or non-carriers). There is only one prospective study demonstrating an elevated risk of breast cancer for MMR gene mutation carriers compared with the general population (standardized incidence ratio 3.95; 95% CI 1.59, 8.13).ConclusionsSince breast cancer is a relatively common disease in the general population, more precise estimates of risk and gene-specific risks will need to utilize large prospective cohort studies with a long follow-up. While current data are inconclusive at a population level, individual tumor testing results suggest that MMR deficiency is involved with breast cancers in some individuals with Lynch syndrome.

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“…The separation of tumors into two large groups, epithelial and non-epithelial, is a popular device [27-31]. It has certain practical advantages for clinicians.…”

Section: Discussionmentioning

confidence: 99%

Modern classification of neoplasms: reconciling differences between morphologic and molecular approaches

Berman

2005

BMC Cancer

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Background: For over 150 years, pathologists have relied on histomorphology to classify and diagnose neoplasms. Their success has been stunning, permitting the accurate diagnosis of thousands of different types of neoplasms using only a microscope and a trained eye. In the past two decades, cancer genomics has challenged the supremacy of histomorphology by identifying genetic alterations shared by morphologically diverse tumors and by finding genetic features that distinguish subgroups of morphologically homogeneous tumors.

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Multiple epithelial and nonepithelial tumors in hereditary nonpolyposis colorectal cancer: characterization of germline and somatic mutations of the MSH2 gene and heterogeneity of replication error phenotypes

Cited by 14 publications

References 28 publications

Meta-Analysis ofMSH6Gene Mutation Frequency in Colorectal and Endometrial Cancers

Meta-Analysis ofMSH6Gene Mutation Frequency in Colorectal and Endometrial Cancers

Risk of breast cancer in Lynch syndrome: a systematic review

Modern classification of neoplasms: reconciling differences between morphologic and molecular approaches

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