Difficulties in recognizing families with Hereditary Non-polyposis Colorectal Carcinoma. Presentation of 4 families with proven mutation

Tanyi, Miklós; Olasz, Judit; Kámory, Enikő; Csuka, Orsolya; Tanyi, János L.; Ress, Zsuzsa; Damjanovich, László

doi:10.1016/j.ejso.2008.01.006

Cited by 8 publications

(15 citation statements)

References 15 publications

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“…All tests were performed after obtaining written informed consent from all patients. The methodology in details was previously published [19][20][21].…”

Section: Methodsmentioning

confidence: 99%

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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“…All tests were performed after obtaining written informed consent from all patients. The methodology in details was previously published [19][20][21].…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2012

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“…an earlier age of onset, Crohn's disease-like lymphocytic infiltration of tumor tissues, increased mucin production and a lower degree of histological differentiation compared with FAP (13). In this case report, 11 patients were male and 3 were female, and the fourth generation was markedly younger than the third generation when their cancers were first diagnosed.…”

Section: Discussionmentioning

confidence: 80%

“…Over time, as general knowledge about HNPCC improved, more and more affected families were reported. The characteristic presentation of HNPCC is frequently right-sided localization, the presence of synchronous and metachronous colorectal carcinomas and its association with other HNPCCrelated extra-colonic tumors, including gastric, endometrial and urinary and biliary tract cancers in afflicted families (13). Pancreatic tumors have been reported in relatives with HNPCC (17).…”

Section: Discussionmentioning

confidence: 99%

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A case of multiple primary malignancies and investigation of family history

Huang¹,

Huang

Huang³

et al. 2012

Oncology Letters

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Abstract. The occurrence of multiple primary malignancies (MPM) in one patient is a rare but increasingly frequent event, partly due to medical advances in diagnosis and therapy. A number of theories have been proposed to explain MPM, but none have been proven. A key risk factor appears to be family history. We present the case of a 43-year-old male with multiple cancers who was first admitted to the hospital for an undifferentiated pleomorphic sarcoma/pleomorphic malignant fibrous histiocytoma (pG2T2bN0Mx stage III) of the right scapula in May 2009. The patient underwent three tumor resections in situ due to tumor recurrence. During the period of chemotherapy and radiotherapy, computed tomography (CT) revealed a 10x10-cm enhancing soft mass of the ascending colon, which was diagnosed as mucinous adenocarcinoma in a pathological report. Laboratory data showed elevated serum levels of carcinoembryonic antigen (CEA, 20.0 µg/l; normal range, 0.0-

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“…Among the mutation carriers two patients had very early tumor manifestation [24]. Two germline mutations were found in each of them.…”

Section: Evaluation Of Genetic Alterations In Hnpcc Suspected Patientsmentioning

confidence: 99%

Significance of genetic instability in development and chemosensitivity of malignant tumors

Olasz¹

2009

Clinical and Experimental Medical Journal

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We set the aim to examine the alterations of the main mismatch repair genes (hMLH1 and hMSH2) in the predisposition to hereditary colorectal cancer, and the influence of these genes on the therapeutic sensitivity of testicular germ-cell tumors. We investigated mutations of the p53 gene in primary head and neck tumors with the view to outline their prognostic values in the clinical outcome and the therapeutic responsiveness. Germline alterations of the MMR genes result in autosomal dominantly inherited predisposition to hereditary nonpolyposis colon carcinoma (HNPCC). We applied Bethesda guidelines to select patients not fulfilling Amsterdam criteria. Our findings demonstrated that causative mutations coupled with single nucleotide polymorphisms have worse prognostic values. The majority of testicular germ cell tumors (TGCTs) are highly sensitive to cisplatin-based chemotherapy, but a small fraction of cases are resistant to the effects of chemotherapy. Although we found a strong correlation between weak or loss of hMLH1 expression and promoter hypermethylation, reduced expression of MMR proteins and MSI have not proved to be predictive markers for chemotherapeutic resistance of TGCTs. The analysis of p53 gene mutations in head and neck tumors revealed a significant trend between the tumor stage progression and the frequency of missense mutations on the DNA-binding surface. We found that patients with other than missense mutations (nonsense, splice mutations, deletions) had more favorable prognosis. Mutational analysis of surgical margins may be of value in the prediction of local recurrence and in the decision for postoperative therapy.

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Difficulties in recognizing families with Hereditary Non-polyposis Colorectal Carcinoma. Presentation of 4 families with proven mutation

Cited by 8 publications

References 15 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 case of multiple primary malignancies and investigation of family history

Significance of genetic instability in development and chemosensitivity of malignant tumors

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