PMID- 9776413
OWN - NLM
STAT- MEDLINE
DCOM- 19981028
LR  - 20220408
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 90
IP  - 19
DP  - 1998 Oct 7
TI  - Specific genetic predictors of chemotherapeutic response and survival in patients 
      with anaplastic oligodendrogliomas.
PG  - 1473-9
AB  - BACKGROUND/METHODS: Gliomas are common malignant neoplasms of the central nervous 
      system. Among the major subtypes of gliomas, oligodendrogliomas are distinguished 
      by their remarkable sensitivity to chemotherapy, with approximately two thirds of 
      anaplastic (malignant) oligodendrogliomas responding dramatically to combination 
      treatment with procarbazine, lomustine, and vincristine (termed PCV). 
      Unfortunately, no clinical or pathologic feature of these tumors allows accurate 
      prediction of their response to chemotherapy. Anaplastic oligodendrogliomas also 
      are distinguished by a unique constellation of molecular genetic alterations, 
      including coincident loss of chromosomal arms 1p and 19q in 50%-70% of tumors. We 
      have hypothesized that these or other specific genetic changes might predict the 
      response to chemotherapy and prognosis in patients with anaplastic 
      oligodendrogliomas. Therefore, we have analyzed molecular genetic alterations 
      involving chromosomes 1p, 10q, and 19q and the TP53 (on chromosome 17p) and 
      CDKN2A (on chromosome 9p) genes, in addition to clinicopathologic features in 39 
      patients with anaplastic oligodendrogliomas for whom chemotherapeutic response 
      and survival could be assessed. RESULTS/CONCLUSIONS: Allelic loss (or loss of 
      heterozygosity) of chromosome 1p is a statistically significant predictor of 
      chemosensitivity, and combined loss involving chromosomes 1p and 19q is 
      statistically significantly associated with both chemosensitivity and longer 
      recurrence-free survival after chemotherapy. Moreover, in both univariate and 
      multivariate analyses, losses involving both chromosomes 1p and 19q were strongly 
      associated with longer overall survival, whereas CDKN2A gene deletions and ring 
      enhancement (i.e., contrast enhancement forming a rim around the tumor) on 
      neuroimaging were associated with a significantly worse prognosis. The inverse 
      relationship between CDKN2A gene deletions and losses of chromosomes 1p and 19q 
      further implies that these differential clinical behaviors reflect two 
      independent genetic subtypes of anaplastic oligodendroglioma. These results 
      suggest that molecular genetic analysis may aid therapeutic decisions and predict 
      outcome in patients with anaplastic oligodendrogliomas.
FAU - Cairncross, J G
AU  - Cairncross JG
AD  - Department of Medical and Experimental Oncology, London Regional Cancer Centre, 
      Ontario, Canada.
FAU - Ueki, K
AU  - Ueki K
FAU - Zlatescu, M C
AU  - Zlatescu MC
FAU - Lisle, D K
AU  - Lisle DK
FAU - Finkelstein, D M
AU  - Finkelstein DM
FAU - Hammond, R R
AU  - Hammond RR
FAU - Silver, J S
AU  - Silver JS
FAU - Stark, P C
AU  - Stark PC
FAU - Macdonald, D R
AU  - Macdonald DR
FAU - Ino, Y
AU  - Ino Y
FAU - Ramsay, D A
AU  - Ramsay DA
FAU - Louis, D N
AU  - Louis DN
LA  - eng
GR  - CA57683/CA/NCI NIH HHS/United States
GR  - CA69285/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (DNA, Neoplasm)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Brain Neoplasms/*drug therapy/*genetics
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human, Pair 1/genetics
MH  - Chromosomes, Human, Pair 10/genetics
MH  - Chromosomes, Human, Pair 17/genetics
MH  - Chromosomes, Human, Pair 19/genetics
MH  - Chromosomes, Human, Pair 9/genetics
MH  - DNA, Neoplasm/genetics
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - *Loss of Heterozygosity
MH  - Male
MH  - Middle Aged
MH  - Oligodendroglioma/*drug therapy/*genetics
MH  - Predictive Value of Tests
MH  - Survival Analysis
MH  - Treatment Outcome
EDAT- 1998/10/17 00:00
MHDA- 1998/10/17 00:01
CRDT- 1998/10/17 00:00
PHST- 1998/10/17 00:00 [pubmed]
PHST- 1998/10/17 00:01 [medline]
PHST- 1998/10/17 00:00 [entrez]
AID - 10.1093/jnci/90.19.1473 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 1998 Oct 7;90(19):1473-9. doi: 10.1093/jnci/90.19.1473.