Explanation slides Knudsons 2 Hit Hypothesis

1. © 2009 NHS National Genetics Education and Development Centre Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Inherited Pre-disposition to Cancer
Knudson’s 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 Centre Genetics and Genomics for Healthcare
www.geneticseducation.nhs.uk
Inherited Pre-disposition to Cancer
These slides show pictorial views of Knudson’s 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 Centre Genetics 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 Centre Genetics 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.