Array Comparative Genomic Hybridization based Identification of Key Genetic Alterations at 2p21-p16.3 (MSH2, MSH6, EPCAM), 3p23-p14.2 (MLH1), 7p22.1 (PMS2) and 1p34.1-p33 (MUTYH) Regions in Hereditary Non Polyposis Colorectal Cancer (Lynch Syndrome) in the Kingdom of Saudi Arabia

In this study, whole genome comparative genomic hybridization array (array CGH) based genomic analysis was performed on twelve Saudi Lynch syndrome patients. A total of 124 chromosomal alterations (structural loss) were identified at mean log2 ratio cut off value of ±0.25. We also found structural loss in 2p21-p16.3, 3p23-p14.2, 7p22.1 and 1p34.1-p33 regions. These findings were subsequently validated by real time quantitative PCR showing downregulation of MSH2, MSH6, EPCAM, MLH1, PMS2 and MUTYH genes. These findings shall help in establishing database for alterations in mismatch repair genes underlying Lynch syndrome in Saudi population as well as to determine the incidence ratio of these disorders. Guided counselling will subsequently lead to the prevention and eradication of Lynch Syndrome in the local population.
Source: Saudi Journal of Biological Sciences - Category: Biology Source Type: research

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Lynch Syndrome (LS) entails a defective DNA mismatch repair system, which is the post-replicative proofreading and editing system, ensuring our genome's integrity. LS predisposes to several cancers, most commonly colorectal and endometrial cancers. LS occurs in approximately 1 in 250 –1,000 people.LS is associated with urological malignancies with upper tract urothelial carcinoma the most common, although still clinically underestimated. Other urologic malignancies possibly associated with LS include bladder, prostate, testis, and renal cell carcinoma.
Source: Urology - Category: Urology & Nephrology Authors: Source Type: research
Abstract Hereditary non-polyposis colorectal cancer (HNPCC) also known as Lynch Syndrome (LS), is a hereditary form of colorectal cancer (CRC). LSis caused by mutations in the mismatch repair (MMR) genes, mostly in MLH1, MSH2, MSH6 and PMS2. Identification of these gene mutations is essential to diagnose CRC, especially at a young age to increase the survival rate. Using open target platform, we have performed genetic association studies to analyze the different genes involved in the LS and to obtain target for disease evidence. We have also analyzed upstream regulators as target molecules in the data sets. We dis...
Source: Bioinformation - Category: Bioinformatics Authors: Tags: Bioinformation Source Type: research
AbstractLynch syndrome is a cancer-predisposing syndrome inherited in an autosomal-dominant manner, wherein colon cancer and endometrial cancer develop frequently in the family, it results from a loss-of-function mutation in one of four different genes (MLH1,MSH2,MSH6, andPMS2) encoding mismatch repair proteins. Being located immediately upstream of theMSH2 gene,EPCAM abnormalities can affectMSH2 and cause Lynch syndrome. Mismatch repair proteins are involved in repairing of incorrect pairing (point mutations and deletion/insertion of simple repetitive sequences, so-called microsatellites) that can arise during DNA replica...
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research
Colorectal cancer (CRC) has many subtypes with different prognoses and response to treatment. Patients must be characterized to access the most appropriate treatment and improve outcomes. An increasing number of biomarkers are required for characterization but are not in routine use. We investigated whether CRC can be stratified routinely within a small district general hospital to inform clinical decision making at local multidisciplinary team meeting/tumor board level. We evaluated mismatch repair (MMR) and EGFR signaling pathways using predominantly in-house immunohistochemical (IHC) tests (MSH2, MSH6, MLH1, PMS2, BRAF-...
Source: Applied Immunohistochemistry and Molecular Morphology - Category: Chemistry Tags: Online Articles: Research Article Source Type: research
Conclusion: In this retrospective study, 0.5% (6/1179) of lung cancer patients were found to harbor a germline mutation on MSH2, MSH6 or PMS2. However, two of these patients displayed intact MMR protein expression, MSS and TMB-L. Combined with the baseline characteristics of 6 patients, it seems that lung cancers may not be related to Lynch syndrome. Relationships between the development of lung cancers and Lynch syndrome still requires further large–scale investigations. Nonetheless paired tumor–normal next-generation sequencing can identify germline mutations including that related with Lynch syndrome in canc...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionDiagnosis of LS was mainly depended on the following: the cancer histories of his relatives, multi ‐primary cancers of lung and stomach in his own body, MLH1 and MSH2 gene mutations detected in the cancer tissues. The clinical significance of this new MLH1 c.1896+5G>A germline mutation detected in the LS ‐associated double primary cancer patient needed further study.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: CLINICAL REPORT Source Type: research
Conclusion: The incremental diagnostic yield decreased substantially after age 70 to 75 years. Stopping reflex CRC screening for LS after age 80 years may be reasonable because of very low efficiency, particularly in resource-limited settings, but this merits further investigation. Studies evaluating the effect of diagnosing LS in elderly persons on their family members are needed. Primary Funding Source: Kaiser Permanente Northern California Division of Research. PMID: 31181578 [PubMed - as supplied by publisher]
Source: Annals of Internal Medicine - Category: Internal Medicine Authors: Tags: Ann Intern Med Source Type: research
ConclusionWe show that low ‐level mosaicism can be detected by using high‐coverage targeted NGS panels on constitutional and/or tumor DNA. This report illustrates that by using sensitive sequencing techniques, more cases of genetic diseases driven by mosaic mutations may be identified, with important clinical consequences for patients and family members.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: CLINICAL REPORT Source Type: research
Lynch syndrome, is an autosomal dominantly inherited disease that predisposes individuals to a high risk of colorectal cancers, and some mismatch-repair genes have been identified as causative genes. The purpo...
Source: BMC Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Case report Source Type: research
AbstractMany colorectal cancers (CRCs) that exhibit microsatellite instability (MSI) are not explained byMLH1 promoter methylation or germline mutations in mismatch repair (MMR) genes, which cause Lynch syndrome (LS). Instead, these Lynch-like syndrome (LLS) patients have somatic mutations in MMR genes. However, many of these patients are young and have relatives with cancer, suggesting a hereditary entity. We performed germline sequence analysis in LLS patients and determined their tumor ’s mutational profiles using FFPE DNA. Six hundred and fifty-four consecutive CRC patients were screened for suspected LS using MS...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
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