Evidence for a clonal origin of head and neck tumors

Abstract According to the inactive‐X hypothesis only one of the two genes at X‐linked loci is active in somatic cells of females. Thus, in women heterozygous for the A and B genes at the X‐linked glucose‐6‐phosphate dehydrogenase (G‐6‐PD) locus, single cells or clones of cells show either type A or type B enzyme. Similarly, pure tumors with a clonal origin arising in G‐6‐PD heterozygotes exhibit only type A or B enzyme, while those with multiple cell origin may show both A and B enzymes. The G‐6‐PD types of normal and neoplastic tissue were determined in 28 patients with tumors of the head and neck who were heterozygous at the G‐6‐PD locus. Normal tissues contained two enzyme types. Only one tumor from the 11 patients with anaplastic carcinoma of the nasopharynx was pure enough (i. e., with a relatively small number of non‐tumor cells) to allow firm conclusions. This tumor had a single enzyme phenotype and this is compatible with a clonal origin. Single enzyme phenotypes were also found in the two benign tumors and in single cases of plasmacytoma, melanoma, neuroblastoma and reticulum‐cell sarcoma. The data from three cases of carcinoma of the palate and from single cases of carcinoma of an ectopic salivary gland and the thyroid gland respectively are also compatible with a clonal origin. Only one relatively pure tumor had a double enzyme phenotype, but even in this case, the evidence for a multiple cell origin is not convincing. Thus, the data in this and other studies suggest that at least one step in the development of most human neoplasms occurs in a single cell, i. e., the mature tumors have a clonal origin.