Extreme phenotypes in in Breast-Ovarian Cancer: Whole exome analysis in very early onset cases
2011-2015 | GSRT

Breast cancer is a very common disease with 6,000 new cases estimated every year in Greece, and 420,000 new cases in Europe  (mortality 130,000/year), while ovarian cancer respective figures are 1,000 and 67,000 with a much higher, proportionally, mortality (42,000/year)  as they are usually diagnosed in later stages.

Breast cancer has a mean age of onset of 54 years and ovarian cancer 64 years. Hereditary cases present a ~12 years earlier mean age of onset, 42 and 52 respectively. Early age of disease onset is indicative of a defect in a cancer predisposing gene. Approximately 2% of breast and ~ 1% of ovarian cancer cases are diagnosed at ages < 30 years, with the youngest diagnosed cases of breast or ovarian cancer being 16 years old. The reasons of cancer presentation at that young age are largely unknown although mutations in many DNA repair genes (e.g. BRCA1, BRCA2, PALB2, CHEK2, RAD51C, p53, STK11, CDH1, PTEN)  can explain at least partially this extreme phenotype. However the age at onset and the severity of the illness are excellent predictors of allelic heterogeneity in new loci yet to be identified.

Based on these considerations our proposed project has the following specific objectives:

  1. Determine the inherited genetic background in 50 breast and 30 ovarian cancer cases with very early onset (17-35yrs) of the disease using next generation sequencing (NGS)
  2. Identify germ line mutations in new cancer genes and determine their impact on the pathogenesis of breast or ovarian carcinomas at a very young age.
  3. Identify modifier genes through NGS in 14 families with multiple cases of breast-ovarian cancer positive for a germ-line mutation in a critical cancer gene but with a wide range (17-50) of disease age at onset.
  4. Perform complete histopathological analysis in all samples and correlate pathology and molecular analysis data
  5. Translate the new findings in clinically relevant procedures
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