Colorectal cancer (CRC)
For several years our oncogenetic research group has been working on projects related to Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome that accounts for approximately 3% of all colorectal cancer cases. The increased risk of developing cancer in HNPCC is nearly always due to an inherited mutation in a mismatch repair (MMR) gene. In HNPCC kindreds the most common cancers are colorectal and endometrial.
We have already established methodology for microsatellite instability (MSI) testing and screening for germline mutations in DNA mismatch-repair genes of patients with HNPCC. A National Register for colorectal cancer was instituted in the University Hospital “Tzaritza Yoanna”, Sofia and more than 400 patients were selected for MSI and loss of heterozygosity (LOH) analysis. The MSI positive tumours were further analyzed for hMLH1 and hMSH2 mutations, hMLH1 promoter hypermethylation and MLH1 protein expression. A significant association has been found between the epigenetic change and MSI/LOH sporadic cases. Additionally, we investigated the role of the hotspot V600E somatic mutation in BRAF gene and its application in the HNPCC screening selection criteria. The mutation screening detected some known and two novel mutations, in both hMLH1 and hMSH2 genes. We developed an efficient diagnostic strategy for HNPCC testing. The association between CRC and polymorphisms in estrogen receptor-alpha (ER-alpha), Vitamin D receptor (VDR) and CHEK2 genes has also been investigated. Screening for K-ras mutations has been performed.
Recently MMC is expanding its abilities by the use of MLPA (Multiplex Ligation-dependent Probe Amplification) in a search for large genomic deletions and duplications.
Prof. Damyan Damyanov, MD, PhD – Department of Surgery, Medical Faculty, Head of Clinic of Surgery and Clinical center of Gastroenterology,
Emil Kostadinov, MD, PhD student - Clinic of Surgery, University Hospital "Tzaritza Yoanna", Sofia;
Assoc. Prof. Maia Galabova, MD, PhD – Vice Dean of Scientific Research,
Assoc. Prof. Tatyana Vlaykova, PhD – Department of Chemistry and Biochemistry,
Maria Angelova, MD – Department of Obstetrics and Gynaecology, Medical Faculty, Trakia University - Stara Zagora;
Assoc. Prof. D.Nedin,MD
Assist. Prof. A. Alexandrova, MD, Military Hospital – Plovdiv;
Milko Mirchev, MD - Clinic of Gastroenterology, University Hospital “St. Marina", Medical University – Varna.