Clustering of colon, lung, and other cancer susceptibility genes with protein tyrosine phosphatases and protein kinases in multiple short genomic regions.

Interactions of large gene families are poorly understood. We found that human, mouse, and rat colon and lung cancer susceptibility genes, presently considered as separate gene families, were frequently pairwise linked. The orthologous mouse map positions of 142 of 159 early discovered colon and lung cancer susceptibility genes formed 41 genomic clusters conserved >70 million years. These linked gene pairs concordantly affected both tumors and their majority was linked with two other gene families - protein tyrosine phosphatases and cancer driver protein kinases. 25% of both protein tyrosine phosphatases and protein kinases mapped <1 cM from a colon or lung cancer susceptibility gene, and 50% in <3 cM. Similar linkage was detected with most other human susceptibility genes that controlled 29 different cancer types. This concentration of tumor susceptibility genes with protein tyrosine phosphatases and driver protein kinases in multiple relatively short genomic regions suggests their possible functional diversity.