Hereditary non‐polyposis colorectal cancer/Lynch syndrome in three dimensions

Kravochuck, Sara E.; Church, James M.

doi:10.1111/ans.13483

Cited by 5 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For hereditary non-polyposis colorectal cancer, Amsterdam criteria, tumor testing for microsatellite instability (MSI) as well as presence of causative mutations in the mis-match repair (MMR) genes, have been used for sub-classification [19]. Overlaps in mutation spectrum between polyposis and non-polyposis syndromes are also recognized.…”

Section: Introductionmentioning

confidence: 99%

Expanding the genotype–phenotype spectrum in hereditary colorectal cancer by gene panel testing

et al. 2016

View full text Add to dashboard Cite

Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel-based approaches detecting both SNVs, indels and CNVs in the same assay. We applied a panel including 19 CRC susceptibility genes to 91 individuals of six phenotypic subgroups. Targeted NGS-based sequencing of the whole gene regions including introns of the 19 genes was used. The individuals had a family history of CRC or had a phenotype consistent with a known CRC syndrome. The purpose of the study was to demonstrate the diagnostic difficulties linked to genotype-phenotype diversity and the benefits of using a gene panel. Pathogenicity classification was carried out on 46 detected variants. In total we detected sixteen pathogenic or likely pathogenic variants and 30 variants of unknown clinical significance. Four of the pathogenic or likely pathogenic variants were found in BMPR1A in patients with unexplained familial adenomatous polyposis or atypical adenomatous polyposis, which extends the genotype-phenotype spectrum for this gene. Nine patients had more than one variant remaining after the filtration, including three with truncating mutations in BMPR1A, PMS2 and AXIN2. CNVs were found in three patients, in upstream regions of SMAD4, MSH3 and CTNNB1, and one additional individual harbored a 24.2 kb duplication in CDH1 intron1.Electronic supplementary materialThe online version of this article (doi:10.1007/s10689-016-9934-0) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

Expanding the genotype–phenotype spectrum in hereditary colorectal cancer by gene panel testing

et al. 2016

View full text Add to dashboard Cite

show abstract

“…En la presente serie, en sólo 23 de las 50 familias con criterios de Amsterdam (46%) pudieron identificarse variantes patogénicas o probablemente patogénicas. Esta incidencia es similar a la comunicada por otros autores [11][12][13][14][15][16] . La identificación de una variante patogénica permite no sólo distinguir entre portadores y no portadores (y por ende focalizar las medidas de prevención), sino también establecer diferentes niveles de riesgos.…”

Section: Discussionunclassified

Síndrome de Lynch: impacto de la caracterización de familias en base a estudios genéticos

Vaccaro

Piñero

Herrando

et al. 2018

RevOnco

View full text Add to dashboard Cite

El objetivo de este trabajo fue caracterizar demográfica y molecularmente las familias con diagnóstico de síndrome de Lynch en base a estudios genéticos. Se utilizó la base prospectiva del Registro de Epidemiología Molecular de Cáncer Colorrectal (REM-CCR) del Hospital Italiano de Buenos Aires (Clinical trials.gov NCT02781337). El criterio de inclusión fue que tuvieran hecho un estudio genético entre 1996 y 2017 (secuenciación y/o determinación de grandes rearreglos de al menos un gen reparador de error de apareamiento). Se analizaron 50 familias con los criterios de Amsterdam. En 23 (46%) se identificaron variantes patogénicas (n=19) y probablemente patogénicas (n=2). El 28.6% de las variantes patogénicas fueron originalmente descritas en esta serie, entre ellas la variante c.1911del en el exón 12 de MSH2 identificada en una familia con agregación de cáncer de mama. Fue identificada una mutación fundadora de Piamonte, Italia (c.2252_2253del). Los genes afectados incluyeron MSH2 (13 variantes)MLH1 (9 variantes) y PMS2 (1 variante). La tasa de detección de mutaciones fue del 46%. Entre las familias con mutación identificada (n=23), se detectó una edad mediana de inicio del cáncer menor (46 vs. 50 años, p=0.02) y mayor incidencia de tumores extra-colorrectales (90.5% vs. 45.8%, p <0.01), que las 27 sin mutaciones. La implementación de estudios genéticos permitió caracterizar variables demográficas en base a la identificación de mutaciones germinales asociadas al síndrome de Lynch, identificándose dos grupos diferenciados por la edad de afectación y la incidencia de tumores extracolónicos.

show abstract

“…For instance, around 60% of Lynch-like CRCs exhibit bi-allelic somatic inactivation of MMR genes within the tumor (32)(33)(34). A somatic mutation in one allele of MMR genes along with loss of heterozygosity of the other allele is the most common described pattern (17,35). These somatic MMR gene mutations are likely sporadic events, suggesting that such tumors are most likely cancers with sporadic DNA MMR deficiency.…”

Section: Lynch-like Syndromementioning

confidence: 99%

“…According to Kravochuck and Church, families with FCCTX do not have a specific syndrome but may have one of several genotypes, including mutY DNA glycosylase (MUTYH)-associated polyposis, nth-like DNA glycosylase 1 (NTHL1)-associated polyposis, polymerase proofreading-associated polyposis, or serrated polyposis (35).…”

Section: Figure 2 Genomic Rearrangement Upstream Of the Muts Homologmentioning

confidence: 99%

Update on Hereditary Colorectal Cancer

Silva

Wernhoff

Dominguez-Barrera

et al. 2016

View full text Add to dashboard Cite

Hereditary non‐polyposis colorectal cancer/Lynch syndrome in three dimensions

Abstract: Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance.

Cited by 5 publications

References 20 publications

Expanding the genotype–phenotype spectrum in hereditary colorectal cancer by gene panel testing

Expanding the genotype–phenotype spectrum in hereditary colorectal cancer by gene panel testing

Síndrome de Lynch: impacto de la caracterización de familias en base a estudios genéticos

Update on Hereditary Colorectal Cancer

Contact Info

Product

Resources

About