1. © 2009 NHS National Genetics Education and Development CentreGenetics and Genomics for Healthcare www.geneticseducation.nhs.uk Inherited Pre-disposition to Cancer Knudsons Two Hit Hypothesis This PowerPoint file contains a number of slides that may be useful for your teaching of genetics concepts. You may use these slides and their contents for non-commercial educational purposes.

2. © 2009 NHS National Genetics Education and Development CentreGenetics and Genomics for Healthcare www.geneticseducation.nhs.uk Inherited Pre-disposition to Cancer These slides show pictorial views of Knudsons Two Hit Hypothesis whilst giving a brief explanation of the development of inherited or familial cancer. The last slide shows a pedigree of a family with predominantly breast cancer, indicating what a clinically high risk pedigree would look like. Of note is the appearance of skipped generations in female individuals I.4 and 1.7, indicating non-penetrance of the familial BRCA gene alteration.

3. © 2009 NHS National Genetics Education and Development CentreGenetics and Genomics for Healthcare www.geneticseducation.nhs.uk The genetic basis of the dominantly inherited familial cancer syndromes Clone of cancer cells from this one cell Inherited altered allele Second allele of the pair becomes inactivated (somatic mutation) An altered allele is inherited and is found in all body cells that contain genetic material. When the second (previously normal) allele of the gene pair becomes inactivated in a particular somatic cell, this can lead to loss of control of cell growth and unchecked cell proliferation.

4. © 2009 NHS National Genetics Education and Development CentreGenetics and Genomics for Healthcare www.geneticseducation.nhs.uk Fig. 12.1 ©Scion Publishing Ltd Photo. courtesy of Dr Gareth Evans. (a)Pedigree of the Wilson family, showing types of cancer and age at diagnosis. (b)Carcinoma of the breast detected in a 40-year-old woman by magnetic resonance imaging. This lady had a BRCA1 mutation.