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Analysis
of 1p, 19q, 9p, and 10q as prognostic markers for high-grade astrocytomas using
fluorescence in situ hybridization on tissue microarrays from Radiation Therapy
Oncology Group trials
Daniel
J. Brat, Wendy F. Seiferheld, Arie Perry, Elizabeth H. Hammond, Kevin J. M Urray,
Alan R. Schulsinger, Minesh P. Mehta, Walter J. Curran
Radiation Therapy Oncology Group (RTOG) Translational Research
Program, Philadelphia, PA: Departments of Pathology and Laboratory Medicine,
Emory University School of Medicine, Atlanta, GA 30322 (D.J.B.); RTOG
Statistical Division, Philadelphia, PA 19107 (W.F.S.); Division of
Neuropathology, Washington University School of Medicine, St. Louis, MO 63110
(A.P.); Department of Pathology, LDS Hospital, Salt Lake City, UT 84143
(E.H.H.); Department of Radiation Oncology, Medical College of Wisconsin,
Milwaukee, WI 53226 (K.J.M.); Department of Radiation Oncology, SUNY Health
Sciences Center, Brooklyn, NY 11203 (A.R.S.); Department of Human Oncology,
University of Wisconsin Medical School, Madison, WI 53792 (M.P.M.); Department
of Radiation Oncology, Jefferson Medical College, Philadelphia, PA 19107
(W.J.C.); USA
Survival
periods vary considerably for patients with high-grade astroctomas, and reliable
prognostic markers are not currently available.
We therefore investigated whether genetic losses from chromosomes 1p, 19p, or
10q were associated with survival in 89 high-grade astrocytomas using tissue
microarrays (TM As) derived from Radiation Therapy Oncology Group clinical
trials.
Cases included 15 anaplastic astrocytomas (AAs) and 74 glioblastomas (GBMs)
selected on the basis of survival times significantly shorter or longer than the
expected median.
Genetic analysis was performed by TMA-fluorescence in situ hybridization (FISH)
on array sections using 8 DNA probes, including those directed at 1p32, 19q13.4,
9p21 (p16/CDKN2A), and 10q (PTEN and DMBT1).
Genetic status for each locus was correlated with patient survival group, and
data were analyzed by using Fisher's exact test of association (adjusted P
= 0.025).
Losses of chromosome 1p, either alone or in combination with 19q, were
encountered in only 2 cases, both AAs.
This contrasts with oligodendrogliomas, in which combined 1p and 19q losses are
frequent and predictive of prolonged survival.
Solitary 19q loss was noted in 3/15 AAs and in 7/70 GBM s and was more frequent
in the long-term survival group (P = 0.041, AA and GBM combined).
Chromosome 9p loss was seen in 5/8 AAs and 39/57 GBM s, whereas chromosome 10q
loss was detected in 4/15 AAs and 48/68 GBMs.
The 9p and 10q deletions were slightly more frequent in short-term survivors,
though none of the comparisons achieved statistical significance.
Long-term and short-term survival groups of high-grade astrocytomas appear to
have dissimilar frequencies of 19q, 9p, and 10q deletions.
TM A-FISH is a rapid and efficient way of evaluating genetic alterations in such
tumors.
© 2004 Duke
University Press
Source:
http://konstanza.ingentaselect.com/vl=7977727/cl=65/nw=1/rpsv/cgi-bin/linker?ini=dup_no&reqidx=/cw/dup/15228517/v6n2/s2/p96
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