Muir-Torre syndrome: a variant of the cancer family syndrome.

Hall, N. R.; Williams, Maurice A.; Murday, Victoria; Newton, Julia A.; Bishop, D. Timothy

doi:10.1136/jmg.31.8.627

Cited by 45 publications

(13 citation statements)

References 35 publications

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“…Because a subset of patients fulfilling these criteria appeared to have hereditary nonpolyposis colon cancer syndrome (HNPCC), a relation between HNPCC and MTS was first suggested by Lynch in 1981 and later strengthened by linkage analyses [Hall et al, 1994;Lynch et al, 1981]. Subsequently, extensive mutation analyses revealed that the same mutations involved in the pathogenesis of HNPCC were also identified in many patients with MTS Entius et al, 2000;Kruse et al, 1996Kruse et al, , 1998Peris et al, 1997].…”

Section: Introductionmentioning

confidence: 93%

Different genetic pathways in the development of periocular sebaceous gland carcinomas in presumptive Muir-Torre syndrome patients

et al. 2006

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Periocular sebaceous gland carcinomas (SGCs) occur in the eyelids either sporadically or as a phenotypic feature of Muir-Torre syndrome (MTS). In knockout mice mismatch-repair (MMR) defects or inactivation of the fragile histidine triad (FHIT) gene are associated with MTS-like signs, including SGC. To dissect the genetic alterations associated with microsatellite instability (MSI) and inactivation of the FHIT gene, we studied nine periocular SGC specimens from MTS patients. Immunohistochemistry was performed for FHIT, MSH2, MLH1, and MSH6. We assessed MSI as well as loss of heterozygosity (LOH) at the FHIT locus with polymorphic markers and genomic multiplex PCR. Epigenetic silencing was detected by methylation-specific PCR (MSP) and combined bisulfite restriction analysis (COBRA). Our analyses identified two SGCs with FHIT positivity and high-grade MSI, and seven cases with loss of FHIT and microsatellite stability (MSS). MSI correlated with loss of MSH2 and MLH1 immunostaining. Loss-of-function mechanisms affecting the FHIT gene were identified as intragenic deletions eliminating the coding exons 5 and 6 on one hand, and complete biallelic methylation of the FHIT transcription regulatory region on the other hand. Germinal FHIT mutations as a predisposing factor for MTS were excluded in two index patients with cancer in three generations, including an FHIT-negative SGC. Our data suggest that either somatic inactivation of the FHIT gene associated with MSS or inactivation of the MMR system resulting in MSI contribute to the development of periocular SGCs in presumptive MTS.

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Section: Introductionmentioning

confidence: 93%

Different genetic pathways in the development of periocular sebaceous gland carcinomas in presumptive Muir-Torre syndrome patients

et al. 2006

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“…4 Eventually, MTS was found to be a variant of HNPCC. 5,6 The pathophysiology involves an autosomally dominant inherited defect in one of the genes encoding the DNA mismatch repair protein (MMRP), resulting in genomic microsatellite instability (MSI). [7][8][9] With a second hit somatic mutation or methylation suppression of the remaining functioning allele, tumors develop.…”

Section: Introductionmentioning

confidence: 99%

Mismatch Repair Protein Deficiency is Common in Sebaceous Neoplasms and Suggests the Importance of Screening for Lynch Syndrome

Plocharczyk¹,

Frankel²,

Hampel

et al. 2013

The American Journal of Dermatopathology

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The association between Lynch syndrome and sebaceous neoplasms is well characterized. The absence of expression of mismatch repair proteins (MMRPs) by immunohistochemistry (IHC) is often used in other Lynch-associated tumors to guide testing. IHC for MLH1, PMS2, MSH2, and MSH6 was performed on 36 benign and malignant sebaceous neoplasms with the absence of one or more MMRP in 38.9% of cases. Among lesions with abnormal IHC, 71.4% were missing both MSH2 and MSH6, 21.4% lacked MLH1 and PMS2, and 7.1% lacked only MSH6. Of the 10 patients with absent MMRP, 5 had gene-test confirmed Lynch syndrome, 3 had no suggestive personal or family medical history and 2 had no recorded data. Tumor-infiltrating lymphocytes in neoplasms with absent MMRP were statistically significantly greater than in those with intact MMRP (16.5 vs. 9.7, P = 0.027). MMRP deficiency is common in sebaceous neoplasms, suggesting the importance of screening for Lynch syndrome in these patients.

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“…Ovarialkarzinom (2,6,8,9) Mammakarzinom (2,7,91 Uterustumoren (8) Prostatakrebs (9) Hodentumor (4) Kolontumoren (7,9) Leberkrebs (1,7) Hirntumoren (5) Leukämie (9) Malignes Melanom (3,7) Cefasel forte …”

Section: In Der Krebstherapieunclassified

“…A third group of families has also been identified that resembles Lynch syndrome II families and is known as the Muir-Torre syndrome. This syndrome in cludes in addition to the spectrum of tumours seen in Lynch syndrome II, benign or malignant lesions of the skin such as sebaceous gland tumours, basal cell carcinomas and keratoacanthomas [6,7]. Very recently, a subset of a fourth syndrome has been linked to HNPCC known as Turcot's syndrome.…”

Section: Hereditary Nonpolyposis Colorectal Cancermentioning

confidence: 99%

DNA Mismatch Repair and Hereditary Nonpolyposis Colorectal Cancer

Scott¹

1997

Oncol Res Treat

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Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited disorder which is characterized by the absence of a premalignant phenotype. Until recently, the only method to identify persons with a predisposition to develop colorectal cancer was by rigorous anamnestic questioning of their family history. The recent discovery that mutations in genes associated with mismatch repair predispose persons to the development of HNPCC has on the one hand provided a more accurate alternative to pedigree analysis but on the other is accompanied by special difficulties with respect to genetic counselling. This review focuses on what is meant by HNPCC, the current knowledge of mismatch repair, mismatch repair gene mutations, their resulting genetic phenotype, its implication in tumour development and screening alternatives for gene carriers.

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Muir-Torre syndrome: a variant of the cancer family syndrome.

Cited by 45 publications

References 35 publications

Different genetic pathways in the development of periocular sebaceous gland carcinomas in presumptive Muir-Torre syndrome patients

Different genetic pathways in the development of periocular sebaceous gland carcinomas in presumptive Muir-Torre syndrome patients

Mismatch Repair Protein Deficiency is Common in Sebaceous Neoplasms and Suggests the Importance of Screening for Lynch Syndrome

DNA Mismatch Repair and Hereditary Nonpolyposis Colorectal Cancer

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