Deoxyribonucleic Acid Mismatch Repair Genes Research Articles

Never too late: Lynch syndrome diagnosed at the age of 71

Lynch syndrome is an autosomal dominantly inherited disease characterized by a mutation in one of the deoxyribonucleic acid mismatch repair genes. In consequence of this defect, patients have higher risk of developing early colorectal and endometrial cancer (among others types of cancer). This syndrome accounts for 3% of all colorectal cancers and 10% to 19% of colorectal cancers diagnosed before the age of 50. Total abdominal colectomy is the best treatment for patients with Lynch syndrome who develop colorectal cancer.

Gastric neuroendocrine hyperplasia and dysplasia in a patient with Lynch syndrome

Lynch syndrome (LS) is a common hereditary syndrome caused by mutations in deoxyribonucleic acid mismatch repair genes, with a high probability of gastrointestinal, gynaecological and other cancers. The most common LS-associated gastric cancer is adenocarcinoma of the intestinal type. Neuroendocrine neoplasia has not been well understood in LS-associated gastric cancer. Herein, we report a case of a 68-year-old female, with a history of Lynch syndrome and ascending colon adenocarcinoma seven years ago, now presenting as synchronous gastric mixed type adenocarcinoma as well as mucinous adenocarcinoma in transverse colon tumour. On histological examination of the resection specimen, we observe additional diffuse neuroendocrine hyperplasia and dysplasia in the background gastric mucosa. As high grade gastric neuroendocrine carcinoma has been reported in Lynch syndrome, our case may indicate the early stage tumourigenesis of the neuroendocrine tumour in Lynch syndrome.

Pancreatic non-functioning neuroendocrine tumor and ,lynch syndrome: a new tumor association

Background: Lynch Syndrome (LS) is a autosomal dominant inheritance caused by a mutation in one of the deoxyribonucleic acid mismatch repair genes. Mutations occur most frequently in the MLH1 and MSH2 genes, followed by MSH6 and then finally PMS2. Colorectal carcinoma (CRC) is the most commonly associated neoplasm. But other neoplasm had been associated: endometrium, gastric, ovarian, breast, small intestine, renal, skin, brain and pancreatic adenocarcinoma. However pancreatic neuroendocrine tumor (PNET), were suggested to be associated but with no confirmation to date. Methods: We present a 65 years old woman affected by LS. She had a CRC 20 year ago. Twelve years later had another one in the right colon. At age of 58 an endometrial cancer was resected. A genetic study was performed and discover a MLH1 MMR gene mutation. She had also a low grade ductal carcinoma of breast at the age of 63 with the same gene mutation. A gastroscopy found a duodenal adenocarcinoma. Results: A pancreaticoduodenectomy was performed. Histology reported a duodenal adenocarcinoma T1N0, two PNET, one G1 and another G2. IHC confirmed the lack of expression of MLH1 and PMS2 in all tumor except in the small PNET. Polymerase chain reaction showed instability only in CRC, duodenal and skin tumors. Conclusion: The association of pancreatic NE tumors and LS is now confirmed and its due to the mutation of the MLH1 and PMS2 nuclear proteins. A gastroscopy with duodenal study should be added in the follow-up of theses patients.

Protein expression profiles of deoxyribonucleic acid mismatch repair genes: Association with clinicopathological characteristics of Malaysian Lynch syndrome patients

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, accounts for approximately 1–5% of all colorectal cancers. Germline mutations in a group of deoxyribonucleic acid (DNA) mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS1, and PMS2) are responsible for Lynch syndrome cases. This study focuses on the determination of MMR (MLH1, MSH2, MSH6, and PMS2) protein expression profile by immunohistochemical analysis and its association with clinicopathological characteristics in clinically diagnosed Malaysian Lynch syndrome patients. Fifty patients who fulfilled any of the revised Bethesda Guidelines criteria were recruited from four collaborating centers in Malaysia. Clinicopathological information of clinically diagnosed Lynch syndrome cases that underwent bowel resection was reviewed. Immunohistochemical analysis for MLH1, MSH2, MSH6, and PMS2 proteins were performed on paraffin-embedded carcinomatous tissues. Colorectal cancer protein expression analysis for MLH1, MSH2, MSH6, and PMS2 antigens showed absence of expression of any MMR proteins in 18 out of 50 clinically diagnosed Lynch syndrome patients (36.0%). There was a significant association between abnormal MMR protein expression with tumor size (p = 0.012), histological differentiation of cancers (p = 0.012), and growth pattern of tumor (p = 0.01). Abnormal expression of MMR protein in colorectal cancers in clinically diagnosed Lynch syndrome patients was associated with specific clinicopathological characteristics such as tumor size, histological differentiation of cancers, and growth pattern of tumor. Immunohistochemical analysis proved to be an advantageous pre-screening tool for Lynch syndrome in Malaysian patients and highly predictive of a germline mutation in DNA MMR genes.

Genetic instability in urinary bladder cancer

Bladder cancer is a major health-care concern. A successful treatment of bladder cancer depends on its early diagnosis at the initial stage. Genetic instability is an essential early step toward the development of bladder cancer. This instability is found more often at the chromosomal level than at the nucleotide level. Microsatellite and chromosomal instability markers can be used as a prognostic marker for screening bladder cancer. Bladder cancer can be distinguished in two different categories according to genetic instability: Cancers with chromosomal level instability and cancers with nucleotide level instability. Deoxyribonucleic acid (DNA) mismatch repair (MMR) system and its correlation with other biologic pathway, both are essential to understand the basic mechanisms of cancer development. Microsatellite instability occurs due to defects in DNA MMR genes, including human mutL homolog 1 and human mutL homolog 2. Chromosomal alterations including deletions on chromosome 3, 8, 9, 11, 13, 17 have been detected in bladder cancer. In the current review, the most recent literature of genetic instability in urinary bladder cancer has been summarized.