Project 3: Tumours
Group Leader: Heli Nevanlinna,PhD
Breast Cancer Research Group has studied the molecular epidemiology of breast cancer susceptibility genes BRCA1 and BRCA2 and evaluated their significance on breast and ovarian cancer in Finland, with direct impact on development of clinical mutation diagnostics and counseling of high-risk breast and ovarian cancer families. The group identified the first major low penetrance predisposition allele (CHEK2 1100delC) for familial breast cancer and also associated with bilateral breast cancer. Another variant of the CHEK2 gene, I157T, is associated with breast cancer risk at the population level and 2.2% of all breast cancer in Finland may be due to this genetic variant. Inherited genetic variation affects also breast cancer progression, drug response and patient survival. The R72P polymorphism of 53 gene significantly associates with histopathological characteristics of the breast tumours and survival of the patients independently of other known prognostic factors. Furthermore, this effect is modulated by a genetic variant in another gene in the same apoptotic pathway, and such genetic variants predict also response to chemotherapy. These results suggest that the identification and clinical management of the carriers of these breast cancer genes and alleles is clinically meaningful.
Ovarian Cancer Research Group ( Chief Investigator Ralf Bützow, MD) is focusing on molecular pathology and therapy of ovarian carcinoma. Ovarian cancer has the highest mortality rate of all gynaecological cancers, and is the 4 th leading cause of death of cancer in women. Ovarian cancer has several well established risk factors linked to reproduction. The group has shown that a) different histological subtypes of ovarian and uterine carcinomas differ in genomic alterations, b) the frequency and pattern of genomic changes in serous carcinomas of Müllerian derivatives (ovary, fallopian tube, uterus) –sporadic or hereditary – are alike, suggesting a common pathway of tumorigenesis, c) the most prominent regions of genetic deletion in serous ovarian carcinoma (distal 8p and distal 18q) have been mapped by allelotyping and the expression of candidate genes and the respective proteins has been characterized. The group has continued molecular characterization and classification of ovarian carcinomas. Recent progress has been made in the characterization of the frequency, correlation to clinicopathological features, and nature (gain-of-function mutation/amplification/gene or protein overexpression/protein activation by phosphorylation) of aberrations in receptor kinases against which molecularly targeted treatment is available (erbB-2, PDGFRA, cKIT, COX-2, EGFR published; others in the pipeline).
Page updated 20 November, 2007