Genetic markers predictive of chemosensitivity and outcome in gliomatosis cerebri.
BACKGROUND
Up-front temozolomide (TMZ) has been recently proposed as a treatment for gliomatosis cerebri (GC), but no predictive or prognostic markers have been identified so far. Because 1p19q codeletion and methylguanine methyl transferase promoter (MGMTP) methylation have been correlated with chemosensitivity of gliomas, their value was investigated in a cohort of patients with GC treated with TMZ.


METHODS
A cohort of 25 GC patients who were treated with TMZ was investigated for 1p19q codeletion and O6-methylguanine DNA.


RESULTS
Patients with a 1p/19q codeletion had a higher response rate (88% [8/9] vs 25% [4/16], p = 0.002), higher progression-free survival (24.5 vs 13.7 months, p = 0.017), and higher overall survival (66.8 vs 15.2 months, p = 0.011) than patients without 1p/19q codeletion. Fourteen of 19 evaluable tumors for MGMTP status were methylated. MGMTP methylation was associated with 1p/19q codeletion (p = 0.045). Patients with unmethylated MGMTP tended to have a shorter progression-free survival and a higher rate of progressive disease.


CONCLUSIONS
Response rate to temozolomide and prognosis seem tightly correlated to 1p19q loss. The impact of methylguanine methyl transferase promoter methylation status on gliomatosis cerebri is still unsettled in this population.
Kaloshi
G
G
Service de Neurologie Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Everhard
S
S
Laigle-Donadey
F
F
Marie
Y
Y
Navarro
S
S
Mokhtari
K
K
Idbaih
A
A
Ducray
F
F
Thillet
J
J
Hoang-Xuan
K
K
Delattre
J-Y
JY
Sanson
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005819:Genetic Markers / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018302:Neoplasms, Neuroepithelial / Q000188:drug therapy* / Q000235:genetics*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide