THE HUMAN GENE MAP IN RELATION TO CANCER Victor A. McKusick, Johns Hopkins University School of Medicine, Baltimore, MD.
Probably now no one would seriously question the statement that all cancers are genetic diseases, i.e., that changes in the genome are necessary ~nd sufficient to lead to the malignant process. Gane mapping has in no small part been re.sponsible for the extensive validation of this hypothesis which was put forward in particularly full form by Theodor Boveri in 1914. The identification of specific microscopically visible changes in the chromosomes associated with specific types of neoplasia, the identification and mapping of oneogenes, and correlation of the two approaches has been responsible for the extensive validation of the Boveri chromosome theory of cancer in recent years. Approximately 1 5 0 0 expressed genes have been mapped to specific chromosome regions. About 4600 genes loci have been identified, either on phenotypic grounds alone (on the basis of Mendelian variation) or in a substantial percentage of eases n o w , by cloning of the gene. Many of the cancer genes have been identified, in the first instance, solely on the basis of their production of transformation or their association with microscopically visible changes in specific neoplasia. The mitochondrial genome has been completely mapped and sequenced and the functions of all its genes are known. A relationship between mutations in the mitochondrial ganome and cancer has not been identified.