CLONAL ANALYSIS OF HUMAN ASTROCYTOMAS

Clonal analysis of many human cancers have generally confirmed that th ey are monoclonal. Although astrocytic neoplasms are the most frequent ly occuring primary tumors in the central nervous system, their clonal composition has not been systematically studied. In this report, the clonal composition of 22 human astrocytomas of all histological grades (2 well-differentiated astrocytomas, 3 anaplastic astrocytomas and 17 glioblastoma multiforme) was determined by analysis of the pattern of X-chromosome inactivation. Leukocyte and non-tumor brain DNA were use d as controls. In addition, specimens from different parts of four gli oblastoma multiforme were analyzed to determine whether remote areas o f the same tumor had the same clonal composition. Eighteen of nineteen informative astrocytomas had a monoclonal pattern of X-chromosome ina ctivation; one glioblastoma multiforme had loss of heterozygosity on t he X chromosome. Specimens from different areas of the same tumor all had identical patterns of X-chromosome inactivation. Leukocytes and no n-tumor brain used as controls uniformly had a polyclonal pattern of X -chromosome inactivation. Furthermore, loss of heterozygosity for chro mosomes 10 or 17 p loci was found in 64% (9/14) of informative specime ns and identical allelic patterns were observed in specimens from diff erent areas of the same tumor. Our results demonstrate that human astr ocytomas from low to high-grade are characterized by monoclonal cell p opulations. The presence of monoclonality in even low-grade neoplasms suggests that in astrocytic tumors the establishment of monoclonality occurs quite early. Also, the finding of a monoclonal pattern in inter mediate- and high-grade astrocytomas further supports the hypothesis t hat clonal expansion underlies astrocytic tumor progression.