Hereditary Colorectal Cancer

Lynch, Henry T.; Chapelle, Albert de la

doi:10.1056/nejmra012242

Cited by 1,857 publications

(1,509 citation statements)

References 87 publications

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“…6,7,[9][10][11][12] MSI is caused by inactivation of the DNA mismatch repair system that may either result from promoter hypermethylation of the DNA mismatch repair gene MLH1 in sporadic carcinogenesis, 13 or following germline mutations in DNA mismatch repair system genes in hereditary nonpolyposis colorectal cancer. 14 CIN involves gains or losses of whole chromosomes and/or chromosomal fractions and is considered to result from defects in chromosomal segregation, telomere stability, and DNA damage repair. 15,16 In B80% of colon cancers, CIN and/or MSI are found.…”

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confidence: 99%

Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP

et al. 2011

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Characterization of tumor genetics and epigenetics allows to stratify a tumor entity according to molecular pathways and may shed light on the interactions of different types of DNA alterations during tumorigenesis. Small intestinal adenocarcinoma is rare, and to date the interrelation of genomic instability and epigenetics has not been investigated in this tumor type. We therefore analyzed 37 primary small bowel carcinomas with known microsatellite instability and KRAS status for chromosomal instability using comparative genomic hybridization, for the presence of aberrant methylation (CpG island methylation phenotype) by methylation-specific polymerase chain reaction, and for BRAF mutations. Chromosomal instability was detected in 22 of 37 (59%) tumors (3 of 9 microsatellite instable, and 19 of 28 microsatellite stable carcinomas). Nine carcinomas (24%) were microsatellite and chromosomally stable. High-level DNA methylation was found in 16% of chromosomal instable tumors and in 44% of both microsatellite instable and microsatellite and chromosomally stable carcinomas. KRAS was mutated in 55, 0, and 10% of chromosomal instable, microsatellite instable, and microsatellite and chromosomally stable tumors, respectively whereas the frequencies of BRAF mutations were 6% for chromosomal instable and 22% for both microsatellite instable and microsatellite and chromosomally stable carcinomas. In conclusion, in this study we show that chromosomal instable carcinomas of the small intestine are distinguished from microsatellite instable and microsatellite and chromosomally stable tumors by a high frequency of KRAS mutations, low frequencies of CpG island methylation phenotype, and BRAF mutations. In microsatellite instable and microsatellite and chromosomally stable cancers, CpG island methylation phenotype and BRAF/KRAS mutations are similarly distributed, indicating common mechanisms of tumor initiation or progression in their molecular pathogenesis.

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confidence: 99%

Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP

et al. 2011

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“…For example, studies indicate that a mutation in a mismatch repair gene is found in approximately 40% to 80% of families that meet the Amsterdam I criteria and only about 5% to 50% of families meeting the Amsterdam II criteria. 15 Similarly, only about 5% to 10%of unselected patients with breast cancer 16 and 20% to 25% of patients with hereditary breast cancer 17 are found to carry a deleterious BRCA1 or BRCA2 mutation. Additionally, a number of other genes associated either with rare high-penetrance syndromes or a more moderate penetrance were identified.…”

Section: Single/limited Gene Testingmentioning

confidence: 99%

How Far Do We Go With Genetic Evaluation? Gene, Panel, and Tumor Testing

Lynce

Isaacs

2016

American Society of Clinical Oncology Educational Book

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OVERVIEW The traditional model by which an individual was identified as harboring a hereditary susceptibility to cancer was to test for a mutation in a single gene or a finite number of genes associated with a particular syndrome (e.g., BRCA1 and BRCA2 for hereditary breast and ovarian cancer or mismatch repair genes for Lynch syndrome). The decision regarding which gene or genes to test for was based on a review of the patient’s personal medical history and their family history. With advances in next-generation DNA sequencing technology, offering simultaneous testing for multiple genes associated with a hereditary susceptibility to cancer is now possible. These panels typically include high-penetrance genes, but they also often include moderate- and low-penetrance genes. A number of the genes included in these panels have not been fully characterized either in terms of their cancer risks or their management options. Another way some patients are unexpectedly identified as carrying a germline mutation in a cancer susceptibility gene is at the time they undergo molecular profiling of their tumor, which typically has been carried out to guide treatment choices for their cancer. This article first focuses on the issues that need to be considered when deciding between recommending more targeted testing of a single or a small number of genes associated with a particular syndrome (single/limited gene testing) versus performing a multigene panel. This article also reviews the issues regarding germline risk that occur within the setting of ordering molecular profiling of tumors.

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“…Quintuple primary cancers are rare 5, 6, 7, 8, 9, 10, 11. We experienced a case of quintuple tumors including LCS.…”

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Cytological findings of langerhans cell sarcoma in a case of quintuple cancer

Tabata

Murata

Takasawa

et al. 2017

Diagnostic Cytopathology

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Langerhans cell sarcoma (LCS) and quintuple cancers are extremely rare. In this report, a case of quintuple cancers including LCS was described. An 80‐year‐old man had squamous cell carcinoma of the nasal skin, colon and rectum adenocarcinomas, and T‐cell/histiocyte‐rich large B‐cell lymphoma. As swelling of multiple submental lymph nodes was observed, fine‐needle aspiration was carried out. Many large cells with high‐grade nuclear atypia and abundant cytoplasm were observed. Lymphocytes and eosinophils were observed in the background. Although a malignant tumor was suspected, a definite diagnosis could not be made. In a biopsy sample, the tumor cells were positive for vimentin, CD68, S‐100, CD1a, and CD163 and negative for epithelial, lymphocyte, and melanoma markers in immunohistochemistry. A diagnosis of LCS was made from the immunohistochemical findings and high mitotic rate with atypical forms. The patient died about 2 months after the first medical examination. Metastasis of LCS was confirmed in many organs by autopsy. LCS has a poor prognosis. In cases with the above‐described cytological findings, LCS should be added to the list of differential diagnosis. The cytological findings presented here may be useful for determining appropriate clinical management such as staging of the disease and follow‐up of the neoplasm. Diagn. Cytopathol. 2017;45:441–445. © 2017 The Authors Diagnostic Cytopathology Published by Wiley Periodicals, Inc.

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Hereditary Colorectal Cancer

Cited by 1,857 publications

References 87 publications

Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP

Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP

How Far Do We Go With Genetic Evaluation? Gene, Panel, and Tumor Testing

Cytological findings of langerhans cell sarcoma in a case of quintuple cancer

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