ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis)

Hegde, Madhuri; Ferber, Mathew; Mao, Rong; Samowitz, Wade S.; Ganguly, Arupa

doi:10.1038/gim.2013.166

Cited by 147 publications

(116 citation statements)

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“…10 • In some centres, screening of exons 3 to 15J (codon 1700) in all patients and exons 1, 2, 15J-W (codons 1700-ter) in case of extradigestive manifestation only. • This is usually done in the context of commercially available or customized gene panels including a number of genes related to the phenotype and its differential diagnoses.…”

Section: Methodsmentioning

confidence: 99%

Clinical Utility Gene Card for: Familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) - update 2014

2014

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Section: Methodsmentioning

confidence: 99%

Clinical Utility Gene Card for: Familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) - update 2014

2014

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“…For example, a silent alteration in exon 14 (c.1869G > T) was reported to cause exon skipping due to its impact on splice enhancer sites [34] . Also the p.I1307K missense mutation in APC, though not causing classic FAP, carries a 10%-20% increased lifelong risk of CRC, but the p.E1317Q missense mutation in APC has an, as yet, uncertain role in colon cancer [20] . Though a minority of patients suspected to have FAP are found to carry VUS, with the increasing availability of APC gene testing and broader testing such as whole exome sequencing, its expected the number of patients with APC VUS will grow.…”

Section: Nondiagnostic and Variants Of Unknown Significance Challengesmentioning

confidence: 99%

“…Identification of a mutation in APC provides molecular confirmation of FAP. The American College of Medical Genetics and Genomics guidelines recommend complete APC gene analysis be considered in any individual with 100 or more colonic polyps, autosomal dominant inheritance and/or extra-colonic manifestations of FAP (e.g., congenital hypertrophy of retinal pigment epithelium, desmoids, gastric fundic gland polyps, among others), when no prior family member has undergone testing [20] . If a familial mutation is identified, targeted APC analysis can be performed [21] .…”

mentioning

confidence: 99%

Genomic era diagnosis and management of hereditary and sporadic colon cancer

Snyder

2014

WJCO

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The morbidity and mortality attributable to heritable and sporadic carcinomas of the colon are substantial and affect children and adults alike. Despite current colonoscopy screening recommendations colorectal adenocarcinoma (CRC) still accounts for almost 140000 cancer cases yearly. Familial adenomatous polyposis (FAP) is a colon cancer predisposition due to alterations in the adenomatous polyposis coli gene, which is mutated in most CRC. Since the beginning of the genomic era next-generation sequencing analyses of CRC continue to improve our understanding of the genetics of tumorigenesis and promise to expand our ability to identify and treat this disease. Advances in genome sequence analysis have facilitated the molecular diagnosis of individuals with FAP, which enables initiation of appropriate monitoring and timely intervention. Genome sequencing also has potential clinical impact for individuals with sporadic forms of CRC, providing means for molecular diagnosis of CRC tumor type, data guiding selection of tumor targeted therapies, and pharmacogenomic profiles specifying patient specific drug tolerances. There is even a potential role for genomic sequencing in surveillance for recurrence, and early detection, of CRC. We review strategies for diagnostic assessment and management of FAP and sporadic CRC in the current genomic era, with emphasis on the current, and potential for future, impact of genome sequencing on the clinical care of these conditions. © 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Colorectal adenocarcinoma; Familial adenomatous polyposis; Genome sequencing; Personalized medicine; Cancer genomics; Pharmacogenomics; Genomic medicine Core tip: The era of genomic sequencing is beginning to make significant impact on the diagnosis and management of sporadic and inherited colorectal adenocarcinoma (CRC) such as familial adenomatous polyposis. This review will discuss the current guidelines for diagnosis and management of CRC and how genomic sequencing is enabling earlier definitive diagnosis with associated intensive surveillance and preventative interventions, molecular tumor characterization directing tumor specific therapy, germline patient genome analysis which informs individual drug tolerance and efficacy, and is evolving to develop post-treatment surveillance, with the potential to ultimately decrease the current prevalence and mortality of CRC, sporadic and hereditary.Esplin ED, Snyder MP. Genomic era diagnosis and management of hereditary and sporadic colon cancer. World J Clin Oncol 2014; 5(5): 1036-1047 Available from: URL: http://www. wjgnet.com/2218-4333/full/v5/i5/1036.htm DOI: http://dx.doi. org/10.5306/wjco.v5.i5.1036 INTRODUCTIONThe annual incidence in the United States of colorectal adenocarcinoma (CRC) is almost 140000 [1] . The morbidi- ty and mortality attributable to heritable and sporadic carcinomas of the colon are substantial and affect children and adults alike, with CRC being the third highest cause of cancer mortality among men and wom...

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“…Full sequencing of APC using Sanger sequencing or next-generation sequencing can be employed to detect the mutations. If no mutations are detected by sequencing, large rearrangement analysis of the gene should be performed [77].…”

Section: Fap and Attenuated Fapmentioning

confidence: 99%

“…Multiplex ligation-dependent probe amplification (MLPA) is commonly used to detect large deletions/rearrangements. Other methods used for large gene rearrangements include Southern blot hybridization, multiplex amplifiable probe hybridization, quantitative PCR analysis, and gene-targeted array-based comparative genomic hybridization [77].…”

Section: Molecular Testing In Hereditary Colorectal Cancer Syndromes mentioning

confidence: 99%

Current applications of molecular pathology in colorectal carcinoma

2017

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Molecular pathology is playing an increasingly important role in the treatment and overall management of patients with colorectal carcinoma. Three distinct genetic pathways have been identified that play a role in carcinogenesis: the chromosomal instability pathway, the microsatellite instability pathway, and the CpG island methylator phenotype pathway. Certain genetic mutations, some of which overlap with the aforementioned pathways, can also indicate that a carcinoma patient has a genetic predisposition syndrome, such as familial adenomatous polyposis, Lynch syndrome, and hamartomatous polyposis syndromes. A variety of advanced methods, including next-generation sequencing, are available to test for these and other mutations, such as targetable mutations that may allow tailoring of a treatment regimen to a patient's specific cancer (e.g., KRAS and BRAF mutations). The possible future role of testing circulating tumor cells is also addressed. New mutations and syndromes continue to be discovered, ensuring that our knowledge of colorectal carcinoma and our ability to treat it will advance in the future.

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ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis)

Cited by 147 publications

References 100 publications

Clinical Utility Gene Card for: Familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) - update 2014

Clinical Utility Gene Card for: Familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) - update 2014

Genomic era diagnosis and management of hereditary and sporadic colon cancer

Current applications of molecular pathology in colorectal carcinoma

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