Clonal composition of human adamantinomatous craniopharyngiomas and somatic mutation analyses of the patched (PTCH), Gs alpha and Gi2 alpha genes

Craniopharyngioma is the most common childhood tumor and thought to arise f rom embryonic remnants of Rathke's pouch. The paucity of published data on the molecular basis of these tumors prompted us to examine 22 adamantinomat ous craniopharyngiomas looking for genetic abnormalities. Using the X-linke d polymorphic androgen receptor gene as a tool for X-chromosome inactivatin g analysis, we found that a subset of craniopharyngiomas are monoclonal and therefore are probably due to acquired somatic genetic defects. Thus, we i nvestigated these tumours for mutations within three candidate genes, Gs al pha, Gi2 alpha and patched (PTCH). Using single stranded conformational pol ymorphism (SSCP), denaturing gradient gel electrophoresis and direct sequen cing, the presence of somatic mutations in these genes could not be demonst rated in any tumor. Our data indicate that a subset of craniopharyngiomas a re monoclonal and the mutations in the PTCH, Gs alpha, and Gi2 alpha contri bute little if any to cranipharyngioma development. (C) 2001 Published by E lsevier Science Ireland Ltd.