Classifying MMR Variants: Time for Revised Nomenclature in Lynch Syndrome

You, Y. Nancy; Vilar, Eduardo

doi:10.1158/1078-0432.ccr-13-0392

Cited by 9 publications

(4 citation statements)

References 12 publications

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“…The terms "Lynch-like syndrome" or "mutation-negative LS" have been used to define tumors with dMMR but no germline pathogenic/ likely pathogenic variant in a MMR gene or EPCAM (Rodríguez-Soler et al, 2013;You & Vilar, 2013). This nomenclature is misleading and any use of the term "Lynch syndrome" for this group should be avoided (Box 1).…”

Section: Nomenclaturementioning

confidence: 99%

Risk assessment and genetic counseling for Lynch syndrome – Practice resource of the National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer

Holter

Hall

Hampel

et al. 2022

Journal of Genetic Counseling

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Identifying individuals who have Lynch syndrome involves a complex diagnostic workup that includes taking a detailed family history and a combination of various tests such as immunohistochemistry and/or molecular which may be germline and/ or somatic. The National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer have come together to publish this practice resource for the evaluation of Lynch syndrome. The purpose of this practice resource was to provide guidance and a testing algorithm for Lynch syndrome as well as recommendations on when to offer testing. This practice resource does not replace a consultation with a genetics professional. This practice resource includes explanations in support of this and a summary of background data. While this practice resource is not intended to serve as a review of Lynch syndrome, it includes a discussion of background information and cites a number of key publications which should be reviewed for a more in-depth understanding. This practice resource is intended for genetic counselors, geneticists, gastroenterologists, surgeons, medical oncologists, obstetricians and gynecologists, nurses, and other healthcare providers who evaluate patients for Lynch syndrome.

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Section: Nomenclaturementioning

confidence: 99%

Risk assessment and genetic counseling for Lynch syndrome – Practice resource of the National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer

Holter

Hall

Hampel

et al. 2022

Journal of Genetic Counseling

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“…Some patients present with clinical suspicion for Lynch syndrome and CRC with microsatellite instability yet lack pathogenic germline mutations in a mismatch repair gene. [30][31][32] These individuals are defined as having mutation-negative Lynch syndrome or Lynch-like syndrome. [30][31][32][33] Their adjusted standardized incidence ratio (SIR) for CRC is 2.12 (95% CI, 1.16 to 3.56), which is lower than that conferred by Lynch syndrome but higher than the population risk.…”

Section: Germline Genetic Predispositionmentioning

confidence: 99%

“…[30][31][32] These individuals are defined as having mutation-negative Lynch syndrome or Lynch-like syndrome. [30][31][32][33] Their adjusted standardized incidence ratio (SIR) for CRC is 2.12 (95% CI, 1.16 to 3.56), which is lower than that conferred by Lynch syndrome but higher than the population risk. 33 Other patients whose family history meets the Amsterdam criteria and who have mismatch repair-proficient CRCs have been diagnosed as having familial CRC syndrome X.…”

Section: Germline Genetic Predispositionmentioning

confidence: 99%

Colorectal Cancer in the Adolescent and Young Adult Population

You

Lee

Deschner

et al. 2020

JCO Oncology Practice

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Colorectal cancer in the young adult population is of increasing incidence and concern. Genetic predisposition and heritable syndromes contribute to this trend, but perhaps more concerning is the majority of new diagnoses that involve no traceable genetic risk factors. Prevention and early recognition, with a high suspicion in the symptomatic young adult, are critical in attenuating recent trends. Clinical management requires coordinated multidisciplinary care from diagnosis to surveillance in order to ensure appropriate management. This review provides a summary of key aspects related to colorectal cancer in adolescents and young adults, including epidemiology, biology, genetics, clinical management, and prevention.

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“…However, not all individuals with MMR-deficient tumors will harbor a germline MMR mutation. This group of patients is known as mutation-negative Lynch syndrome or Lynch-like syndrome [3, 4] and many are due to biallelic somatic mutations in the MMR genes [5–7]. However, germline mutations undetectable by traditional sequencing or MLPA deletion/duplication analyses are also a potential cause.…”

Section: Introductionmentioning

confidence: 99%

Identification of MSH2 inversion of exons 1–7 in clinical evaluation of families with suspected Lynch syndrome

et al. 2016

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Purpose Traditional germline sequencing and deletion/duplication analysis does not detect Lynch syndrome-causing mutations in all individuals whose colorectal or endometrial tumors demonstrate mismatch repair (MMR) deficiency. Unique inversions and other rearrangements of the MMR genes have been reported in families with Lynch syndrome. In 2014, a recurrent inversion of MSH2 exons 1-7 was identified in five families suspected to have Lynch syndrome. We aimed to describe our clinical experience in identifying families with this specific inversion. Methods Four probands whose Lynch syndrome-associated tumors demonstrated absence of MSH2/MSH6 staining and who had negative MMR germline testing were evaluated for the MSH2 inversion of exons 1-7, offered during initial genetic workup or upon routine clinical follow-up. Results All four probands tested positive for the MSH2 inversion. Proband cancer diagnoses included colon and endometrial adenocarcinoma and sebaceous adenoma. A variety of Lynch syndrome-associated cancers were reported in the family histories, although only one family met Amsterdam II criteria. Thirteen at-risk relatives underwent predictive testing. Conclusion MSH2 inversion of exons 1-7 was found in four probands previously suspected to have Lynch syndrome based on family history and tumor testing. This testing should be offered routinely to patients with tumors demonstrating loss of MSH2/MSH6 staining.

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Classifying MMR Variants: Time for Revised Nomenclature in Lynch Syndrome

Cited by 9 publications

References 12 publications

Risk assessment and genetic counseling for Lynch syndrome – Practice resource of the National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer

Risk assessment and genetic counseling for Lynch syndrome – Practice resource of the National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer

Colorectal Cancer in the Adolescent and Young Adult Population

Identification of MSH2 inversion of exons 1–7 in clinical evaluation of families with suspected Lynch syndrome

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