1p/19q Loss of Heterozygoty Patterns in Infiltrative Gliomas
KA Durand, NI Weinbreck, AN Guillaudeau, IS Pommepuy, FR Caire, SA Robert, AL Chaunavel, FJ Labrousse. Dupuytren University Hospital, Limoges, France
Background: Loss of heterozygoty (LOH) of 1p and 19q chromosomal arms has been mainly reported in oligodendrogliomas. 1p/19q codeletion is currently considered as a reliable predictive and/or prognostic marker. However, reported deletion patterns are variable: telomeric, interstitial, centromeric or involving whole arms. Consequently, their identification depends on the method used, particularly with LOH and FISH assays. In addition, prognosis could differ according to the 1p deletion pattern.
Design: We studied 1p and 19q deletion patterns in 42 gliomas. There were: 19 astrocytomas, 1 grade II (AII), 6 grade III (AIII) and 12 glioblastomas (GB); 14 oligodendrogliomas, 7 grade II (OII) and 7 grade III (OIII); 9 oligoastrocytomas, 4 grade II (OAII) and 5 grade III (OAIII). LOH was assessed by PCR and capillary electrophoresis on histologically selected areas from paraffin blocks vs. blood DNA, using 16 and 7 microsatellite markers spanning the entire arms (from centromere to telomere) of 1p and 19q chromosomes, respectively.
Results: We identified 5 molecular patterns: whole arm deletion (wLOH), telomeric deletion (tLOH), interstitial deletion, scattered deletion and no LOH. 1p wLOH was linked to the histological type (p=0.0006): presence in 64% of the oligodendrogliomas (9/14) without correlation with grade (p=0.35); presence in only one mixed OAIII; absence in all the AII, AIII and GB. 1p wLOH was strongly associated with 19q wLOH (p<0.0001) and this whole 1p/19q deletion was restricted to the 9 oligodendrogliomas. A 1p tLOH was found in 1 AIII, 1 OIII and 2 OAIII that was associated with a 19q tLOH in 1 OAIII. All but one of these tumors recurred within a year and had a worse prognosis than the other tumors of same histology. The other molecular patterns were not correlated with histological type and grade while 12 astrocytic tumors had no LOH.
Conclusions: Our study points out the usefulness of an entire 1p and 19q chromosome arms analysis. Our results confirm that whole 1p/19q codeletion is a marker of classical oligodendrogliomas although there is no strict concordance between histological and molecular data since this codeletion is absent in about one third of cases. The presence of a 1p/19q wLOH in OII as well as in OIII may indicate that this molecular alteration is an early event in oligodendroglioma carcinogenesis. Regarding prognosis, tLOH could be pejorative and we suggest that results of LOH and FISH assays targeted only on the telomeric regions should be carefully interpreted.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 189, Tuesday Morning