The spectrum of Lynch syndrome-associated germ-line mutations in Russia.

This study aimed to investigate the spectrum of germ-line mutations in Russian LS patients. LS-related mismatch repair (MMR) genes were analyzed in 16 patients, who were forwarded to genetic testing due to strong clinical features of LS and had high-level microsatellite instability (MSI-H) in the tumor (n = 14) or unknown MSI status (n = 2). In addition, 672 consecutive colorectal cancer (CRC) cases were screened for family history; 15 patients were younger than 50 years and reported 2 or more instances of LS-related cancers in 1st- or 2nd-degree relatives. Seven of these cases demonstrated MSI-H and therefore were subjected to DNA germ-line testing. Overall, 17/23 (74%) subjects carried LS-associated gene variants (MLH1: 10; MSH2: 4; MSH6: 2; PMS2: 1), with 2 alleles (MLH1 c.677G > T and MSH2 с.1906G > C) detected twice. Testing for recurrent mutations of 30 consecutive MSI-H CRCs led to the identification of 2 additional subjects with LS. The analysis of all relevant publications identified 28 unrelated LS patients presented in Russian medical literature and 3 unrelated Russian LS subjects described in international journals. Overall, 15/49 (31%) genetic defects revealed in Russian LS patients were represented by six recurrent alleles (MLH1: c.350C > T, c.677G > T, c.1852_1854del; MSH2: c.942+3A > T, c.1861C > T, с.1906G > C). We conclude that the founder effect ...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research

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This review is an appraisal of the current state of knowledge of 2 enigmatic histotypes of ovarian carcinoma: endometrioid and clear cell carcinoma. Both show an association endometriosis and the hereditary nonpolyposis colorectal cancer (Lynch) syndrome, and both typically present at an early stage. Pathologic and immunohistochemical features that distinguish these tumors from high-grade serous carcinomas, each other, and other potential mimics are discussed, as are staging, grading, and molecular pathogenesis.
Source: Surgical Pathology Clinics - Category: Pathology Authors: Source Type: research
Abstract Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of only 8% and is estimated to be the second leading cause of cancer-related deaths by 2021. Prior convention held that screening for PDAC would not be beneficial; however, a deeper understanding of the carcinogenesis pathway supports a potential window of opportunity among the target population. Screening for PDAC is not a standard practice among the general population because of its low incidence. However, screening may be beneficial for individuals with familial history, chronic diseases with genetic predispositions, or inherited cancer...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research
Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of only 8% and is estimated to be the second leading cause of cancer-related deaths by 2021. Prior convention held that screening for PDAC would not be beneficial; however, a deeper understanding of the carcinogenesis pathway supports a potential window of opportunity among the target population. Screening for PDAC is not a standard practice among the general population because of its low incidence. However, screening may be beneficial for individuals with familial history, chronic diseases with genetic predispositions, or inherited cancer syndromes, such a...
Source: American Journal of Pathology - Category: Pathology Authors: Tags: Review Source Type: research
This article presents a rare clinical of a 61-year-old female diagnosed with extracolonic Lynch syndrome with six metachronous tumours acquiring in digestive tract during the period from 1993 to 2014 (over 21 years). No other cases of six primary malignancies in patient with Lynch syndrome have been reported in literature. Upon diagnosis of Lynch syndrome, it is important to screen patient for malignancies of different localization as this syndrome predisposes appearance of various cancers at earlier age than in general population. PMID: 28938854 [PubMed - as supplied by publisher]
Source: Acta Chirurgica Belgica - Category: Surgery Tags: Acta Chir Belg Source Type: research
Authors: Abstract Ovarian cancer is the second most common type of female reproductive cancer, and more women die from ovarian cancer than from cervical cancer and uterine cancer combined. Currently, there is no strategy for early detection of ovarian cancer that reduces ovarian cancer mortality. Taking a detailed personal and family history for breast, gynecologic, and colon cancer facilitates categorizing women based on their risk (average risk or high risk) of developing epithelial ovarian cancer. Women with a strong family history of ovarian, breast, or colon cancer may have hereditary breast and ovarian canc...
Source: Obstetrics and Gynecology - Category: OBGYN Tags: Obstet Gynecol Source Type: research
Lynch syndrome (hereditary nonpolyposis colorectal cancer) is an autosomal dominant disorder characterized by a significant risk of colorectal and endometrial cancers. A variety of other epithelial cancers may be associated with this syndrome, including ovarian, gastric, small bowel, hepatobiliary, renal, ureteral, skin, breast, prostate, and pancreatic cancers. Brain tumors are infrequent, but have been reported in series [1]. Individuals who have biallelic Lynch syndrome mutations in MLH1, MSH-2, MSH-6, or PMS-2 have a childhood-onset disorder now referred to as constitutional mismatch repair deficiency syndrome, in whic...
Source: Clinical Neurology and Neurosurgery - Category: Neurosurgery Authors: Tags: Case Report Source Type: research
In a recent note, I discused some theories about why the incidence of colonic cancer is increasing in younger patients (see:Why the Increased Incidence of Colonic Cancer Among Younger Americans?). Continuing in this same vein, a recent article I came across raised the issue of multigene panel testing to reveal genetic mutations in the roughly one-third of patents with early onset colonic cancer (see:Multigene Panel Testing Reveals Mutations in One-Third of Early Onset CRC Patients). Below is an excerpt from the article:Although the overall incidence of colorectal cancer (CRC) has been decreasing in the Unite...
Source: Lab Soft News - Category: Laboratory Medicine Authors: Tags: Clinical Lab Industry News Clinical Lab Testing Lab Industry Trends Lab Processes and Procedures Medical Research Preventive Medicine Source Type: blogs
Abstract Hereditary breast ovarian cancer and Lynch/hereditary nonpolyposis colorectal cancer syndrome account for most hereditary gynecologic cancers. In the absence of effective cancer screening and other preventative strategies, risk-reducing surgery in women who are known to be at genetic risk of BRCA-associated or of Lynch syndrome carcinomas is effective in significantly decreasing the lifetime risk of developing malignancy. Reflex genomic testing of high-grade ovarian cancers and reflex immunohistochemistry in endometrial cancers will lead to greater recognition of germline-associated cancers. Approaches to...
Source: Clinical Colorectal Cancer - Category: Cancer & Oncology Authors: Tags: Surg Pathol Clin Source Type: research
Hereditary breast ovarian cancer and Lynch/hereditary nonpolyposis colorectal cancer syndrome account for most hereditary gynecologic cancers. In the absence of effective cancer screening and other preventative strategies, risk-reducing surgery in women who are known to be at genetic risk of BRCA-associated or of Lynch syndrome carcinomas is effective in significantly decreasing the lifetime risk of developing malignancy. Reflex genomic testing of high-grade ovarian cancers and reflex immunohistochemistry in endometrial cancers will lead to greater recognition of germline-associated cancers.
Source: Surgical Pathology Clinics - Category: Pathology Authors: Source Type: research
Authors: Vellone VG, Paudice M, Varesco L Abstract Early diagnosis and proper management of gynecologic malignancies represent a challenge in modern oncology. A growing interest has arisen around the gynecological manifestations of hereditary cancer syndromes. In particular, the discovery of the BRCA1 and BRCA2 genes in ovarian cancer and the mismatch repair genes (MMR) in endometrial carcinoma has revolutionized our approach to the diagnosis and screening of women for ovarian and uterine cancers. The clinical, genetic and pathological features of hereditary cancer syndromes with gynecological manifestations are re...
Source: Minerva Ginecologica - Category: OBGYN Tags: Minerva Ginecol Source Type: research
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