Biallelic germline mutations of mismatch‐repair genes

Poley, Jan–Werner; Wagner, Anja; Hoogmans, Monique M. C. P.; Menko, Fred H.; Tops, Carli M.J.; Kros, Johan M.; Reddingius, Roel E.; Meijers-Heijboer, Hanne; Kuipers, Ernst J.; Dinjens, Winand N.M.

doi:10.1002/cncr.22697

Cited by 87 publications

(19 citation statements)

References 28 publications

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“…Café-au-lait macules are common, seen among 70% of individuals with inherited biallelic MMR mutations, and the presence of colon polyposis has been reported as well. The average age of onset of colon cancer is around 15–16 years, and the average age of onset of small bowel cancer is 20 years 143,144…”

Section: Emerging Issuesmentioning

confidence: 99%

The genetic basis of Lynch syndrome and its implications for clinical practice and risk management

Cohen¹,

Leininger²

2014

TACG

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Lynch syndrome is the most common cause of hereditary colon cancer, and accounts for as much as 3% of all colon and endometrial cancers. The identification and management of individuals with Lynch syndrome have evolved over the past 20 years, yet the syndrome remains vastly underdiagnosed. It is important for clinicians to recognize individuals and families who are at risk in order to be able to manage them appropriately and reduce their morbidity and mortality from this condition. This review will touch on the history of Lynch syndrome, the current knowledge of genotype–phenotype correlations, the cancers associated with Lynch syndrome, and management of individuals who are gene carriers.

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Section: Emerging Issuesmentioning

confidence: 99%

The genetic basis of Lynch syndrome and its implications for clinical practice and risk management

Cohen¹,

Leininger²

2014

TACG

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“…Lynch syndrome also presents rare cases of biallelic mutations [89]. Both homozygosity and compound heterozygosity for MMR deficiency are not lethal while they cause early onset disease manifestations, which includes a neurofibromatosis-like phenotype ( cafè au lait spots) often associated with leukemia or lymphoma, and cerebral and gastrointestinal malignancies [90].…”

Section: Genotype-phenotype Correlation In Lynch Syndromementioning

confidence: 99%

Anticipation in Lynch Syndrome: Where We Are Where We Go

Bozzao

Lastella²,

Stella³

2011

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Lynch syndrome (LS) is the most common form of inherited predisposition to develop cancer mainly in the colon and endometrium but also in other organ sites. Germline mutations in DNA mismatch repair (MMR) gene cause the transmission of the syndrome in an autosomal dominant manner. The management of LS patients is complicated by the large variation in age at cancer diagnosis which requires these patients to be enrolled in surveillance protocol starting as early as in their second decade of life. Several environmental and genetic factors have been proposed to explain this phenotypic heterogeneity, but the molecular mechanisms remain unknown. Although the presence of genetic anticipation in Lynch syndrome has been suspected since 15 years, only recently the phenomenon has been increasingly reported to be present in different cancer genetic syndromes including LS. While the biological basis of earlier cancer onset in successive generations remains poorly known, recent findings point to telomere dynamics as a mechanism significantly contributing to genetic anticipation in Lynch syndrome and in other familial cancers. In this review, we summarize the clinical and molecular features of Lynch syndrome, with a particular focus on the latest studies that have investigated the molecular mechanisms of genetic anticipation.

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“…Mice possessing germline mutation of both alleles display a cancer phenotype differing from that of LS with lymphoma and skin tumors along with GI tract tumors that are predominantly small intestinal. This phenotype is nearly identical to that seen in children and adolescents that carry biallelic germline mutations of the MMR genes [73,74]. …”

Section: Lynch Syndromementioning

confidence: 59%

Chemoprevention in patients with genetic risk of colorectal cancers

2012

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SUMMARY A number of genetic syndromes are known to convey a high risk of colorectal cancer. Current standards of medical practice for these patients involve genetic testing followed by screening and surgical procedures. Pharmaceutical therapies for any of these syndromes are limited in number and are generally not approved by any regulatory body for applications in these genetic groups. This review discusses advances in mechanistic understanding of the disease processes leading to the development of promising pharmaceutical therapies. Clinical trials of potential chemotherapeutic agents must focus on the reduction of disease-related events, including cancer and cancer-related mortality, in patients with genetic syndromes.

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Biallelic germline mutations of mismatch‐repair genes

Cited by 87 publications

References 28 publications

The genetic basis of Lynch syndrome and its implications for clinical practice and risk management

The genetic basis of Lynch syndrome and its implications for clinical practice and risk management

Anticipation in Lynch Syndrome: Where We Are Where We Go

Chemoprevention in patients with genetic risk of colorectal cancers

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