Guidelines for surveillance of individuals with constitutional mismatch repair-deficiency proposed by the European Consortium “Care for CMMR-D” (C4CMMR-D)

Vasen, Hans F. A.; Ghorbanoghli, Zeinab; Bourdeaut, Franck; Cabaret, Odile; Caron, Olivier; Duval, Alex; Entz‐Werlé, Natacha; Goldberg, Yael; Ilenčíková, Denisa; Kratz, Christian P.; Lavoine, Noémie; Loeffen, Jan; Menko, FH; Muleris, Martine; Sébille, G.; Colas, Chrystelle; Burkhardt, B; Brugières, Laurence; Wimmer, Katharina

doi:10.1136/jmedgenet-2013-102238

Cited by 178 publications

(214 citation statements)

References 56 publications

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“…Strict, intensive life-saving cancer surveillance is recommended for any individual with Lynch syndrome . Enrollment in specialised registries and attendance at familial, high-risk gastrointestinal cancer clinics can facilitate the long-term care of such patients Vasen et al, 2014). There is no role for prophylactic colectomy, but prophylactic hysterectomy and bilateral salpingo-oophorectomy should be considered in women who have completed childbearing or after age 40 years as it significantly reduces the risk of both endometrial and ovarian cancer (Schmeler et al, 2006;Vasen et al, 2013).…”

Section: Rev Ised Bethesda Guidelinesmentioning

confidence: 99%

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Ryan

Sheahan

Creavin

et al. 2017

Critical Reviews in Oncology/Hematology

100

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Section: Rev Ised Bethesda Guidelinesmentioning

confidence: 99%

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Ryan

Sheahan

Creavin

et al. 2017

Critical Reviews in Oncology/Hematology

100

118

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“…A high rate of consanguinity is observed especially among homozygous cases (17), whereas in Western countries, most of the cases are associated with composite heterozygous mutation in families with no consanguinity (12). In contrast to family members with LS, many of the heterozygous parents will not be affected, especially among families with PMS2 or MSH6 mutations (14,18).…”

Section: Clinical Presentation Of Cmmrdmentioning

confidence: 99%

“…These tumors occur even in the first decade of life, although sarcomas and genitourinary cancers are also observed in the second decade. CMMRD may present with synchronous or metachronous malignancies of different types (17). Overall, most patients will be affected during childhood (11,12), and the median survival after diagnosis of the primary tumor is less than 30 months (12).…”

Section: Clinical Presentation Of Cmmrdmentioning

confidence: 99%

Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood

Tabori

Hansford

Achatz

et al. 2017

Clinical Cancer Research

185

202

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Replication proofreading is crucial to avoid mutation accumulation in dividing cells. In humans, proofreading and replication repair is maintained by the exonuclease domains of DNA polymerases and the mismatch repair system. Individuals harboring germline mutations in genes involved in this process are at increased risk of early cancers from multiple organs. Biallelic mutations in any of the four mismatch repair genes MSH2, MSH6, MLH1, and PMS2 result in one of the most aggressive childhood cancer predisposition syndromes, termed constitutional mismatch repair deficiency or constitutional mismatch repair deficiency syndrome (CMMRD). Data gathered in the last decade allow us to better define the clinical manifestations, tumor spectrum, and diagnostic algorithms for CMMRD. In this article, we summarize this information and present a comprehensive consensus surveillance protocol for these individuals. Ongoing research will allow for further definition of replication repairdeficient cancer syndromes, assessing the cost-effectiveness of such surveillance protocols and potential therapeutic interventions for these children and families. Clin Cancer Res; 23(11); e32-e37. Ó2017 AACR.See all articles in the online-only CCR Pediatric Oncology Series.

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“…However, neither our patient nor other patients with CMMRD tested so far had a pathogenic germline mutation for NF-1. 5 Leukemia, lymphoma, brain tumors, glial tumors, rhabdomyosarcoma, neuroblastoma, and Wilms tumor are commonly reported in both NF-1 and CMMRD. Currently, it is known that the phenotype of NF-1 and CMMRD may be indistinguishable.…”

Section: Discussionmentioning

confidence: 99%

Colorectal Cancer due to Constitutional Mismatch Repair Deficiency Mimicking Neurofibromatosis I

et al. 2015

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Colorectal carcinoma (CRC) is an extremely rare tumor of childhood that can be associated with cancer predisposition syndromes. A patient with CRC related to constitutional mismatch repair deficiency (CMMRD) syndrome with features of neurofibromatosis type 1 (NF-1) is presented here. A 13-year-old boy was admitted for a 4-month history of diarrhea and rectal bleeding. The patient had extensive café au lait spots, freckling, and Lisch nodules. He fulfilled the NF-1 diagnostic criteria. Colonoscopy showed numerous polyps and a colorectal mass lesion, of which a biopsy revealed adenocarcinoma, an uncommon pathology associated with NF-1. High microsatellite instability and homozygous mutation of PMS2 gene in tumor tissue and blood lymphocytes, respectively, confirmed the diagnosis of CMMRD. Unfortunately, because family history related to CMMRD was negative, the parents denied the diagnosis and refused the therapy, and the patient was lost to follow-up. CMMRD is a rare cancer predisposition syndrome with phenotypical features resembling NF-1. The disease may be suspected in the setting of NF-1 features and CRC, high-grade brain tumors, or hematologic malignancies. Lack of family history related to CMMRD may be a major obstacle to convincing parents of the presence of an inherited disease in their progeny.The DNA mismatch repair (MMR) system is a key pathway contributing to maintenance of genomic stability. The system recognizes, removes, and restores base substitution and insertion-deletion mismatches during DNA replication. 1 In case of MMR deficiency, erroneously inserted nucleotides give rise to high microsatellite instability, which may result in a distinct spectrum of cancers.MLH1, MSH6, MSH2, and PMS2 genes are involved in the mismatch repair system. Heterozygous mutations of these genes cause the autosomal dominant Lynch syndrome (LS), which predisposes typically to colorectal cancer (CRC), usually after the fourth decade of life. Biallelic mutations of MMR genes cause a distinct autosomal recessively inherited cancer predisposition, namely constitutional mismatch repair deficiency (CMMRD) syndrome. 2 The neoplastic spectrum of CMMRD includes hematologic malignancies, central nervous system tumors, and CRCs at an earlier age than expected. Since the first case reported in 1999, 146 cases of CMMRD from 91 families have been documented. Many patients with CMMRD have café au lait spots (CLS) and other features of neurofibromatosis type 1 (NF-1) such as freckling, neurofibromas, Lisch nodules, tibia pseudoarthrosis, sphenoid wing dysplasia, and optic glioma. 3 Lisch nodules are very rare (5 in 146), and the number of CLS does not always reach diagnostic criterion for NF-1 in majority of patients. Here we report the case of a patient with CMMRD and CRC, without familial CASEA 13-year-old boy presented with rectal bleeding and diarrhea of 4 months' duration. Personal history was unremarkable except poor school performance. His parents were firstdegree cousins. No family history of cancer was described. Fam...

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Guidelines for surveillance of individuals with constitutional mismatch repair-deficiency proposed by the European Consortium “Care for CMMR-D” (C4CMMR-D)

Cited by 178 publications

References 56 publications

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood

Colorectal Cancer due to Constitutional Mismatch Repair Deficiency Mimicking Neurofibromatosis I

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