The Molecular Basis of Lynch-like Syndrome

Vargas-Parra, Gardenia; Navarro, Matilde; Pineda, Marta; Capellà, Gabriel

doi:10.1007/978-3-319-74259-5_2

Cited by 3 publications

(3 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because of their biological similarities and responses to treatment, one may suggest to consider all MSI CRC cases as LS, if so most cases would not be inherited. If considering families with clinically dominantly inherited MSI tumours as LS, not all families have demonstrable pathogenic MMR variants [32]. Variants in additional DNA repair genes cause urothelial cancer [31].…”

Section: What Is Lynch Syndrome?mentioning

confidence: 99%

The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care

Møller

2020

Hered Cancer Clin Pract

View full text Add to dashboard Cite

The aims of the Prospective Lynch Syndrome Database (PLSD) are to provide empirical prospectively observed data on the incidences of cancer in different organs, survival following cancer and the effects of interventions in carriers of pathogenic variants of the mismatch repair genes (path_MMR) categorized by age, gene and gender. Although PLSD is assumption-free, as with any study the ascertainment procedures used to identify the study cohort will introduce selection biases which have to be declared and considered in detail in order to provide robust and valid results. This paper provides a commentary on the methods used and considers how results from the PLSD reports should be interpreted. A number of the results from PLSD were novel and some in conflict with previous assumptions. Notably, colonoscopic surveillance did not prevent colo-rectal cancer, survival after colo-rectal, endometrial and ovarian cancer was good, no survival gain was observed with more frequent colonoscopy, new causes of cancer-related death were observed in survivors of first cancers due to later cancers in other organs, variants in the different MMR genes caused distinct multi-cancer syndromes characterized by different penetrance and phenotypes. The www.PLSD.eu website together with the InSiGHT database website (https://www.insight-group.org/variants/databases/) now facilitate evidence-based personalized precision health care for individual carriers at increased risk of cancer. The arguments are summarized in a final discussion on how to conceptualize current knowledge for the different practical purposes of treating cancers, genetic counselling and prevention, and for understanding /research on carcinogenetic mechanisms.

show abstract

Section: What Is Lynch Syndrome?mentioning

confidence: 99%

The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care

Møller

2020

Hered Cancer Clin Pract

View full text Add to dashboard Cite

show abstract

“…MMR proteins may cooperate with other components involved in other DNA repair pathways and thus, MMR deficiency in patients with LLS is likely due to the aberrations in other genes involved in DNA repair. 49 For example, in one patient with LLS, a P variant in RAD51C was detected. This gene is involved in homologous recombination-mediated DNA doublestrand break repair and functions in concert with BRCA1/2 to ensure genomic stability.…”

Section: Discussionmentioning

confidence: 99%

“…There are multiple and redundant DNA repair pathways within the cells and many components, which are organized in multimeric structures, coordinate DNA repair. MMR proteins may cooperate with other components involved in other DNA repair pathways and thus, MMR deficiency in patients with LLS is likely due to the aberrations in other genes involved in DNA repair 49 . For example, in one patient with LLS, a P variant in RAD51C was detected.…”

Section: Discussionmentioning

confidence: 99%

Survey of germline variants in cancer‐associated genes in young adults with colorectal cancer

Mikaeel

Young

et al. 2021

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Colorectal cancer (CRC) incidence in young adults is rising. Identifying genetic risk factors is fundamental for the clinical management of patients and their families. This study aimed to identify clinically significant germline variants among young adults with CRC. Whole‐exome sequencing data of blood‐derived DNA from 133 unrelated young CRC patients (<55 years of age) underwent a comprehensive analysis of 133 cancer‐predisposition/implicated genes. All patient tumors were evaluated for mismatch repair deficiency (dMMR). Among 133 patients (aged 16–54 years), 15% (20/133) had clinically actionable pathogenic or likely pathogenic (P/LP) variants in at least 1 well established cancer‐predisposing gene: dMMR genes (6), MUTYH [bi‐allelic (2), mono‐allelic (3)], RNF43 (1), BMPR1A (1), BRCA2 (4), ATM (1), RAD51C (1), and BRIP1 (1). Five patients (4%) had variants in genes implicated in cancer but where the significance of germline variants in CRC risk is uncertain: GATA2 (1), ERCC2 (mono‐allelic) (1), ERCC4 (mono‐allelic) (1), CFTR (2). Fourteen (11%) had dMMR tumors. Eighteen (14%) reported a first‐degree relative with CRC, but only three of these carried P/LP variants. Three patients with variants in polyposis‐associated genes showed no polyposis (one each in MUTYH [bi‐allelic], RNF43, and BMPR1A). Approximately one in five young adults in our series carried at least one P/LP variant in a cancer‐predisposing/implicated gene; 80% of these variants are currently considered clinically actionable in a familial cancer setting. Family history and phenotype have limitations for genetic risk prediction; therefore multigene panel testing and genetic counseling are warranted for all young adults with CRC regardless of those two factors.

show abstract

References

2021

Constitutional Oncogenetics

View full text Add to dashboard Cite

show abstract

The Molecular Basis of Lynch-like Syndrome

Cited by 3 publications

References 92 publications

The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care

The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care

Survey of germline variants in cancer‐associated genes in young adults with colorectal cancer

References

Contact Info

Product

Resources

About