Promotability and tissue specificity of hereditary cancer genes: Do hereditary cancer patients have a reduced requirement for tumor promotion because all their somatic cells are heterozygous at the predisposing locus?
✍ Scribed by Christos Paraskeva; Ann C. Williams
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 461 KB
- Volume
- 5
- Category
- Article
- ISSN
- 0899-1987
No coin nor oath required. For personal study only.
✦ Synopsis
INITIATION/PROMOTION AND TUMOR SUPPRESSION
Two important concepts in carcinogenesis have stimulated major research programs that have led to significant progress in our understanding of the cellular and molecular basis of cancer. The first is the multistage nature of carcinogenesis and the separation of carcinogenesis into at least two stages: initiation and promotion [I]. The second is Knudson's two-hit hypothesis and the prediction of the existence of tumor suppressor genes [2]. By trying to bring concepts from both these research fields together, in a previous hypothesis paper, we raised the possibility that differences in the cellular microenvironment of the target organs in sporadic-and hereditary-cancer patients could result in fewer events, different events or both being involved in the development of hereditary versus sporadic tumors. We argued that differences in the microenvironment due to all cells in the hereditary-cancer patients being abnormal could, a t least in part, be responsible for the high number and early onset of tumors seen in hereditary-cancer patients [3]. This argument was developed for colorectal carcinogenesis, but could apply equally to all cancers.
In the context of the recent isolation of new tumor suppressor genes, we would like to develop this hypothesis further and to discuss (i) one possible explanation for the tissue specificity of hereditary cancers, (ii) the possibility that hereditary cancers can, a t least in part, bypass or have a reduced dependence on tumor promoters for clonal expansion, and (iii) what kind of predisposing genes are likely to be highly selected for during tumorigenesis, i.e., what makes a gene a good cancer-predisposing gene? The latter point may go some way toward explaining the tissue specificity of certain hereditary cancers. To develop our discussions further in this paper, it is first necessary to lay down the groundwork from our original hypothesis paper [3].
ADENOMAS DO NOT SHOW LOSS OF
H ETE ROZYGOSITY Colorectal cancer occurs in both sporadic and hereditary forms. The most studied hereditary form is familial adenomatous polyposis (FAP; also called familial polyposis coli).