© 2004 by Society
© 2004 by the Society forNeuro-Oncology
Analysis of 1p, 19q, 9p, and 10q as prognostic markers for high-gradeastrocytomas using fluorescence in situ hybridization on tissue microarraysfrom Radiation Therapy Oncology Group trials
Radiation Therapy Oncology Group (RTOG) TranslationalResearch Program, Philadelphia, PA: Departments of Pathology and LaboratoryMedicine, Emory University School of Medicine, Atlanta, GA 30322(D.J.B.); RTOG Statistical Division, Philadelphia, PA19107 (W.F.S.); Division of Neuropathology, WashingtonUniversity School of Medicine, St. Louis, MO 63110 (A.P.); Department of Pathology, LDS Hospital, Salt Lake City, UT84143 (E.H.H.); Department of Radiation Oncology,Medical College of Wisconsin, Milwaukee, WI 53226 (K.J.M.); Department of Radiation Oncology, SUNY Health SciencesCenter, Brooklyn, NY 11203 (A.R.S.); Department ofHuman Oncology, University of Wisconsin Medical School, Madison, WI 53792(M.P.M.); Department of Radiation Oncology, JeffersonMedical College, Philadelphia, PA 19107 (W.J.C.); USA
2 Address correspondence to Daniel J. Brat, Department of Pathology andLaboratory Medicine, Emory University Hospital H-176, 1364 Clifton Road NE,Atlanta, GA 30322(dbrat{at}emory.edu).
| Abstract |
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Survival periods vary considerably for patients with high-gradeastrocytomas, and reliable prognostic markers are not currently available. Wetherefore investigated whether genetic losses from chromosomes 1p, 19q, 9p, or10q were associated with survival in 89 high-grade astrocytomas using tissuemicroarrays (TMAs) derived from Radiation Therapy Oncology Group clinicaltrials. Cases included 15 anaplastic astrocytomas (AAs) and 74 glioblastomas(GBMs) selected on the basis of survival times significantly shorter or longerthan the expected median. Genetic analysis was performed by TMA-fluorescencein situ hybridization (FISH) on array sections using 8 DNA probes, includingthose directed at 1p32, 19q13.4, 9p21 (p16/CDKN2A), and 10q(PTEN and DMBT1). Genetic status for each locus wascorrelated with patient survival group, and data were analyzed by usingFisher's exact test of association (adjusted P = 0.025). Losses ofchromosome 1p, either alone or in combination with 19q, were encountered inonly 2 cases, both AAs. This contrasts with oligodendrogliomas, in whichcombined 1p and 19q losses are frequent and predictive of prolonged survival.Solitary 19q loss was noted in 3/15 AAs and in 7/70 GBMs and was more frequentin the long-term survival group (P = 0.041, AA and GBM combined).Chromosome 9p loss was seen in 5/8 AAs and 39/57 GBMs, whereas chromosome 10qloss was detected in 4/15 AAs and 48/68 GBMs. The 9p and 10q deletions wereslightly more frequent in short-term survivors, though none of the comparisonsachieved statistical significance. Long-term and short-term survival groups ofhigh-grade astrocytomas appear to have dissimilar frequencies of 19q, 9p, and10q deletions. TMA-FISH is a rapid and efficient way of evaluating geneticalterations in such tumors.
Received May 21, 2003; Accepted September 24, 2003
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