Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mono-allelic germline mutations in mismatch repair (MMR) genes lead to Lynch syndrome, an autosomal dominant syndrome with an increased risk of predominantly colorectal and endometrial cancers. Bi-allelic germline mutations in MMR genes predispose to haematological malignancies, brain tumours, gastrointestinal tumours, polyposis and features of neurofibromatosis type 1 in early childhood.We report a brother and a sister with bi-allelic germline mutations in MSH2; a pathogenic deletion of the first 6 exons and a variant of the initiation codon (c.1A>G (p.Met1?)), whereas their phenotypes (four colorectal cancers, small bowel carcinoma and 15 adenomas at age 39 and 48, and colorectal cancer, endometrial cancer and four adenomas at age 33 and 44, respectively) are more suggestive of a mono-allelic pathogenic MMR gene mutation. The carcinomas showed microsatellite instability in the presence of MLH1, PMS2, MSH2 and MSH6 proteins, indicating that the variant c.1A>G leads to an alternative protein with reduced activity that is retained in the tumours.Our data suggest that the MSH2 variant c.1A>G (p.Met1?) should not be considered as a regular pathogenic mutation that leads to a strongly increased cancer risk, though it possibly contributes to a more severe phenotype when combined with a truncating mutation on the other allele.
 ...
PMID:Compound heterozygosity for two MSH2 mutations suggests mild consequences of the initiation codon variant c.1A>G of MSH2. 1878 Nov 92

This article reviews the main molecular alterations involved in endometrial carcinoma. Five molecular features (microsatellite instability, and mutations in the PTEN, k-RAS, PIK3CA and beta-catenin genes) are characteristic of endometrioid carcinomas, whereas non-endometrioid carcinomas show alterations of p53, loss of heterozygosity (LOH) on several chromosomes, as well as other molecular alterations (STK15, p16, E-cadherin and C-erb B2). The review also covers the phenomenon of apoptosis resistance, as well as the results obtained from cDNA array studies, and the perspectives for targeted therapies. A group of practical applications of molecular pathology techniques are also mentioned: diagnosis of hereditary non-polyposis colon cancer syndrome in patients with endometrial carcinoma; evaluation of precursor lesions; prognosis; diagnosis, particularly for synchronous endometrioid carcinomas of the uterus and the ovaries; and targeted therapies.
 ...
PMID:Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints. 1897 6

MUTYH-associated polyposis (MAP) is an autosomal recessive condition predisposing to colorectal cancer, caused by constitutional biallelic mutations in the base excision repair (BER) gene MUTYH. Colorectal tumours from MAP patients display an excess of somatic G>T mutations in the APC and KRAS genes due to defective BER function. To date, few extracolonic manifestations have been observed in MAP patients, and the clinical spectrum of this condition is not yet fully established. Recently, one patient with a diagnosis of endometrial cancer and biallelic MUTYH mutations has been described. We here report on two additional unrelated MAP patients with biallelic MUTYH germline mutations who developed endometrioid endometrial carcinoma. The endometrial tumours were evaluated for PTEN, PIK3CA, KRAS, BRAF and CTNNB1 mutations. A G>T transversion at codon 12 of the KRAS gene was observed in one tumour. A single 1bp frameshift deletion of PTEN was observed in the same sample. Overall, these findings suggest that endometrial carcinoma is a phenotypic manifestations of MAP and that inefficient repair of oxidative damage can be involved in its pathogenesis.
 ...
PMID:Endometrial cancer and somatic G>T KRAS transversion in patients with constitutional MUTYH biallelic mutations. 1898 Aug

Hereditary non-polyposis colorectal cancer is a cancer predisposition syndrome known to be caused by heterozygous germline mutations in DNA mismatch repair genes (MMR) most commonly hMLH1, hMSH2, hMSH6. Heterozygous mutations in one of these genes confer an increased risk, mainly for colon and endometrial cancer. Recently, several publications identified that biallelic mutations in the MMR genes are associated with a more severe phenotype, including childhood malignancies and signs of neurofibromatosis type I (NF1). We report on a non-consanguineous Ashkenazi Jewish family with two affected siblings with features of NF1, colon cancer and astrocytoma at age 13 and 14. Their mother developed endometrial cancer at age 54. Their father had leukoplakia of the vocal cords with a family history of pancreatic cancer. Molecular and pathology studies were done on the tumor tissue and on genomic DNA of family members. Tumor testing demonstrated a high degree of microsatellite instability (MSI analysis), expression of MLH1 and absence of expression of both MSH2 and MSH6 proteins. A biallelic c.1906G > C (p.A636P) mutation in the hMSH2 gene was detected in the blood of one affected child. Parental genetic testing showed that each parent was heterozygote for the mutation. The c.1906G > C mutation is a founder mutation in the Ashkenazi Jewish population. To our knowledge this is the first report of homozygosity for this founder mutation.
 ...
PMID:Homozygosity of MSH2 c.1906G-->C germline mutation is associated with childhood colon cancer, astrocytoma and signs of Neurofibromatosis type I. 1910 24

Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant inherited predisposition to a number of epithelial cancers, most notably colorectal and endometrial cancer. Outside of the context of Lynch syndrome there is little evidence for an autosomal dominant or recessive condition that predisposes to endometrial cancer. Recently, genetic variants in MUTYH have been associated with a recessive form of colorectal cancer, known as MUTYH associated polyposis or MAP. MUTYH is involved in base excision repair of DNA lesions and as such a breakdown in the fidelity of this process would necessarily not be predicted to result in a specific disease. At present there is little information about the role of MUTYH in other types of cancer and only one report indicating a possible relationship with endometrial cancer.Similar to a previous study, we investigated a series of endometrial cancer patients to determine if MUTYH variants were over-represented compared to a series of healthy control subjects and to assess whether or not endometrial cancer risk could be explained by an autosomal recessive model of inheritance.Two MUTYH mutations, Y165C and G382D, and three common MUTYH polymorphisms, V22M, Q324H and S501F, were genotyped in 213 endometrial cancer patients and 226 controls from Australia using real time PCR. Differences in genotype frequencies were compared using Chi-squared analysis and by calculating odds ratios and 95% confidence intervals.Three endometrial cancer patients were identified with heterozygous MUTYH mutations (two G382D and one Y165C). No bi-allelic mutation carriers were identified. Two of the three patients' clinical characteristics were similar to those commonly identified in HNPCC and lend support to the notion that MUTYH mutations increase the risk of developing HNPCC related diseases. There was no difference in the five genotype frequencies of the endometrial cancer patients compared to the controls. The results of our study suggest that MUTYH is unlikely to be involved in the genetic basis of endometrial cancer but a possible association of MUTYH variants with HNPCC related diseases cannot be excluded.
 ...
PMID:Genetic variants in MUTYH are not associated with endometrial cancer risk. 1933 76

Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited disease caused by a germline mutation of the mismatch repair (MMR) genes, and the distinctive feature is that colorectal and extracolonic malignancies occur early in life. We report on the case of a Korean HNPCC family with endometrial cancer, with the goal of elucidating the involvement of an MMR deficiency. Although the family history did not fulfill the Amsterdam criteria II, blood samples were subjected to genetic testing by the revised Bethesda guidelines. Immunohistochemistry and direct sequencing of the genomic DNA identified a C insertion at the 1780th base in exon 16 of hMLH1, a pathogenic mutation that has not been reported before. By this mutation, premature termination at codon 592 resulted with an estimated deletion of 21% of the C-terminus of the hMLH1 protein. For early detection of the disease, the family was examined by colonoscopy and a gynecologic examination. The expression of hMLH1 in colon tissues was analyzed by Western blot analysis. We observed that the C-terminus portion of the hMLH1 protein was truncated in the HNPCC family members. Two young family members with no clinical symptoms were newly diagnosed with colorectal cancer by colonoscopy and a pathological examination. Hereby, we identified a novel pathogenic germline mutation of hMLH1 in a Korean HNPCC family. The loss of C-terminus of hMLH1 protein was thus considered to possibly play a role in the development of HNPCC with other tumors. Our findings might be useful for early diagnosis and management of the HNPCC family.
 ...
PMID:A novel germline mutation of hMLH1 in a Korean hereditary non-polyposis colorectal cancer family. 1936 Mar 43

Studies on mutations and mutation frequencies of the MSH6 gene, which mainly focus on new types of mutations in small samples, have been published ever since the first report of MSH6 mutation in two atypical hereditary non-polyposis colorectal cancer patients. However, the results remain inconsistent. Therefore, a systematic review was conducted and a meta-analysis was undertaken to determine the frequency of MSH6 mutation in colorectal and endometrial cancers. From 27 studies, 180 cases with MSH6 mutation in a total of 3196 cases were detected. In colorectal and endometrial cancers the MSH6 mutation frequency is 7.2 and 9.6%, respectively. MSH6 mutation frequency was 10.4% in hereditary non-polyposis colorectal cancer patients, 7.1% in atypical hereditary non-polyposis colorectal cancer patients, and 5.9% in sporadic patients. The frequency of MSH6 mutation in high microsatellite instability (MSI-H) was 11.6% and in low microsatellite instability (MSI-L) cases was (13.3%), which were higher than in microsatellite stability (MSS) cases (1.7%). The mean age of the earliest onset of colorectal and endometrial cancers in MSH6 mutation carriers was 51.2 and 56.5 yr, respectively. Data suggest that the frequency of MSH6 mutation is higher in hereditary non-polyposis colorectal cancer patients than in atypical hereditary non-polyposis colorectal cancer and sporadic patients. MSH6 mutation frequency was also higher in endometrial than colorectal cancers. The mean age of earliest onset of endometrial cancer (56.5 yr) is older than for colorectal cancer (51.2 yr) in carriers of MSH6 mutation. Our results provide evidence for clinical genetic testing and counseling.
 ...
PMID:Meta-analysis of MSH6 gene mutation frequency in colorectal and endometrial cancers. 1949 30

In women with hereditary non polyposis colorectal carcinoma (HNPCC) an annual gynaecological surveillance has been recommended because of an increased lifetime risk of developing endometrial and ovarian carcinoma. The aim of this study was to assess the efficacy of gynaecological surveillance with regard to endometrial and ovarian carcinoma. Included were women from families that fulfilled the revised Amsterdam criteria for HNPCC or who showed a proven mutation in one of the mismatch repair genes. An annual gynaecological surveillance was performed (transvaginal ultrasound (TVU) and CA 125 assessment). From January 2006 on, routine endometrial sampling was included. In a total number of 100 women 285 surveillance visits were performed. Among these, in 64 visits routine endometrial samplings were performed: three atypical hyperplasias and one endometrial carcinoma were diagnosed. This was significantly more than the atypical hyperplasia and two endometrial carcinomas that were detected after 28 samples performed because of abnormal surveillance results in 221 visits. There were no interval carcinomas. One invasive ovarian carcinoma stage IIIC was diagnosed at ovarian surveillance. Endometrial surveillance with routine endometrial sampling in women with HNPCC is more efficient in diagnosing endometrial (pre)malignancies than TVU only. Ovarian surveillance is not capable of diagnosing early stage ovarian carcinoma. Prophylactic hysterectomy in HNPCC should be restricted to women in whom abdominal surgery for other reasons is performed and to those with particularly increased risk such as MSH6 mutation carriers and/or women with multiple relatives with endometrial carcinoma.
 ...
PMID:Improvement of endometrial biopsy over transvaginal ultrasound alone for endometrial surveillance in women with Lynch syndrome. 1950 73

Women with hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome have a high risk for endometrial cancer (EC) and frequently present with a gynaecological cancer as their first or sentinel malignancy. Identification of these patients is important given their personal and family risk for synchronous and metachronous tumours. Modalities to detect ECs for the possibility of HNPCC include microsatellite instability assay, immunohistochemistry for DNA mismatch repair proteins, MLH1 promoter hypermethylation assay and mutational analysis of DNA mismatch repair genes. The revised Bethesda guidelines provide screening criteria for HNPCC in colorectal cancers (CRCs). However, there are currently no such screening recommendations for women with endometrial carcinoma. While age and family history are useful screening criteria, their sensitivity has been shown to be low for detection of HNPCC in EC. Expansion of these criteria to include tumour morphology (presence of tumour infiltrating lymphocytes and tumour heterogeneity including dedifferentiated/undifferentiated ECs) and topography (lower uterine segment localisation) as well as presence of synchronous ovarian clear cell carcinomas may significantly enhance the detection of patients with EC at risk for HNPCC. Consideration should be given to incorporating these screening criteria into a revision of the Bethesda guidelines for detecting EC patients at highest risk for HNPCC.
 ...
PMID:Lynch syndrome (hereditary non-polyposis colorectal cancer) and endometrial carcinoma. 1963 37

Lynch Syndrome (LS), also known as Hereditary Non-polyposis Colorectal Cancer (HNPCC), is the most common hereditary colorectal cancer syndrome and is estimated to account for 3-5% of CRC cases. LS is caused by mutations in DNA mismatch repair (MMR) genes which are inherited in an autosomal dominant pattern and are associated with accelerated development of cancers. Families affected with Lynch Syndrome typically contain multiple individuals affected with CRC and/or endometrial cancer, with many of the cases diagnosed at younger ages. Lifetime risk for colorectal and endometrial cancers approaches 70-80% and 40-60% respectively, in the absence of medical intervention. Individuals with Lynch Syndrome also have an increased risk for developing other cancers and variations in clinical presentation can make diagnosis difficult. Clinical genetic testing has identified mutations in the MMR genes MLH1, MSH2, MSH6, and PMS2 in many families with Lynch Syndrome. Colonoscopy at frequent intervals has been shown to be effective in reducing morbidity and mortality from Lynch-associated colorectal cancer.
 ...
PMID:Lynch Syndrome/Hereditary Non-polyposis Colorectal Cancer (HNPCC). 2019 Jul 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>