A new mutation in Muir-Torre syndrome associated with familiar transmission of different gastrointestinal adenocarcinomas

Tanyi, Miklós; Olasz, Judith; Lukács, G; Tanyi, János L.; Tóth, László; Antal‐Szalmás, Péter; Ress, Zsuzsa; Bubán, T.; András, Csilla; Damjanovich, László

doi:10.1016/j.ejso.2009.03.011

Cited by 10 publications

(4 citation statements)

References 11 publications

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“…The aim of our group is to fill the gap, since there are very few published data from Hungary [21,[24][25][26][27][28]. Our institution has screened close to 1,500 patients to date and found 11 previously known pathogenic mutations and numerous unclassified variants.…”

Section: Discussionmentioning

confidence: 97%

Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families

et al. 2012

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Lynch syndrome (Hereditary nonpolyposis colorectal cancer, HNPCC) is an inherited disease with variable phenotype causing the development of colon cancer and other malignancies. The basis of the disease is believed to be the mismatch repair gene mutations. Genetic screening has been performed among the patients who have undergone surgery for colon cancer at the University of Debrecen, Department of Surgery. Tumor samples of the screened patients were submitted to immunohistochemistry on hMLH1, hMSH2 and hMSH6 genes, microsatellite instability testing, followed by sequencing and multiple ligation dependent probe amplification. Three families were identified with the missense mutation c.143A>C (p.Q48P) of hMLH1 gene. In one of the families a segregation analysis of this particular variant was also accomplished. The segregation analysis revealed a clear correlation between the tumor cases and the occurrence of this mutation. However, none of the analyzed 100 healthy controls demonstrated the same aberration. There is only one published evidence in the literature about the presence of this rare variant in any population. The Gln to Pro switch in the ATPase domain, a conservative region of the hMLH1 gene, creates significant changes in the protein structure. These results indicate that this mutation is the abnormality responsible for the patients' phenotype and it is feasible that this particular aberration occurs more frequently among Hungarian Lynch syndrome patients.

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Section: Discussionmentioning

confidence: 97%

Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families

et al. 2012

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“…Our data support evidence on a significant contribution from large deletions/duplications in EPCAM and frameshift variants in MLH1 and MSH2 . Of the 220 MMR variants, 178 were already listed in the InSiGHT database or previous studies [ 78 , 79 ], whereas 41 have not been previously reported in LS [ 80 ]. In addition, we observed that MSH2 variants most frequently caused disease in Argentinean LS families.…”

Section: Discussionmentioning

confidence: 99%

A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America

et al. 2017

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BackgroundGenetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America. MethodsEleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome.ResultsWe performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet.ConclusionThe Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.

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“…Therefore, some authors advocate genito-urinary surveillance in addition to upper and lower gastrointestinal endoscopy for all patients with sebaceous tumors [ 10 ]. The presence of sebaceous skin lesions can support the earlier diagnosis of HNPCC in families [ 11 ]. Less commonly, the sebaceous tumors are associated with breast, hematologic, endometrial, and gastric malignancies.…”

Section: Discussionmentioning

confidence: 99%

Muir-Torre Syndrome Presenting as Sebaceous Adenocarcinoma and Invasive MSH6-Positive Colorectal Adenocarcinoma

et al. 2016

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Muir-Torre syndrome (MTS) is a rare genodermatosis, diagnosed by the presence of sebaceous neoplasms along with an internal malignancy, most commonly colorectal carcinomas. MTS is most commonly caused by microsatellite instabilities of the hMLH1 and hMSH2 mismatch repair genes, and is rarely caused by mutations of the hMSH6 gene. We describe the case of a 56-year-old male who presented with an enlarging mass on his back as well as hematochezia. The back mass was excised, and pathology confirmed microsatellite instability in MSH2 and MSH6. Abdominal CT and colonoscopy confirmed the presence of synchronous masses in the cecum, ascending colon, and the transverse colon. He refused any further workup or treatment, only to return 8 months later complaining of hematochezia and discomfort due to an enlarging mass protruding from the rectum. After consenting to surgical intervention, he agreed to outpatient chemotherapy treatment. The presence of sebaceous neoplasms should raise suspicion for the possibility of an associated internal malignancy.

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A new mutation in Muir-Torre syndrome associated with familiar transmission of different gastrointestinal adenocarcinomas

Cited by 10 publications

References 11 publications

Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families

Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families

A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America

Muir-Torre Syndrome Presenting as Sebaceous Adenocarcinoma and Invasive MSH6-Positive Colorectal Adenocarcinoma

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