Somatic Mutations in Cancer This PowerPoint file contains a number of slides that may be useful for teaching of genetics concepts. You may use these slides and their contents for non-commercial educational purposes.

Fig. 12.6 ©Scion Publishing Ltd The relation between sporadic and inherited forms of the same tumour. The target tissue contains n cells and the chance of one cell suffering a loss of function mutation in the tumour suppressor gene is µ. Fig. 12.6 ©Scion Publishing Ltd

Fig. 12.7 ©Scion Publishing Ltd Mechanisms in retinoblastoma. The initial mutation may be inherited or somatic. Mechanisms A, B and D result in loss of heterozygosity (in B, only for markers close to the RB locus; in D only for markers distal to the crossover). In Cavenee’s original study, some tumours duplicated the remaining copy of chromosome 13 after loss of the wild-type chromosome by mechanism A. Fig. 12.7 ©Scion Publishing Ltd

Fig. 12.15 ©Scion Publishing Ltd A possible common pathway for the development of colon cancer. The scheme (see Kinzler and Vogelstein, 19996) summarises the way that some genes are often inactivated in early lesions, while others are inactivated only in late-stage lesions. There has been some controversy about the general applicability of this scheme, and there is no suggestion that every colon cancer has developed exactly in this way. Fig. 12.15 ©Scion Publishing Ltd

The genetic basis of sporadic cancer Both alleles of a gene become inactivated in a particular somatic cell leading to loss of control of growth and unchecked cell proliferation. Clone of cancer cells from this one cell

The genetic basis of the dominantly inherited familial cancer syndromes An altered allele is inherited and so is in all body cells containing genetic material. When the second (previously normal) allele of the gene pair becomes inactivated in a particular somatic cell this leads to loss of control of growth and unchecked cell proliferation. Second allele of the pair becomes inactivated Clone of cancer cells from this one cell Inherited altered allele

Mosaicism * mutation in single gene * chromosomal anomaly Mosaicism can be: somatic (ie in most body cells) or gonadal (confined solely to the gonads).

Somatic mosaicism (eg trisomy 21) as a result of mitotic non-disjunction Mitosis Non-disjunction Normal disomy Normal disomy Trisomy Monosomy (lethal to cell)