Analysis of some rare cancer suggests that due to heterozygosity for an inherited loss-of-function in the tumour suppressor gene. A cancer develops only if a second mutation occurs in the somatic cells and if this mutation knocks out the function of the wild type allele of the tumour suppressor gene. Thus development of cancer requires two loss-of- function mutations- that is, two inactivating “hits” one in each of the two copies of the tumour suppressor gene. In 1971 A. Knudson proposed this explanation for the occurrance of retinoblastoma, a rare, childhood cancer of the eye. Besides this, about 1% of all cancers are hereditary. However, more than 20 different inherited cancer syndromes have been identified. In nearly all of them are due to defect in tumour suppressor genes function rather than due to oncogenes.