Molecular profile of oligodendrogliomas in young patients

Abstract

Several studies on molecular profiling of oligodendrogliomas (OGs) in adults have shown a distinctive genetic pattern characterized by combined deletions of chromosome arms 1p and 19q, O6-methylguanine-methyltransferase (MGMT) methylation, and isocitrate dehydrogenase 1 (IDH1) mutation, which have potential diagnostic, prognostic, and even therapeutic relevance. OGs in pediatric and young adult patients are rare and have been poorly characterized on a molecular and biological basis, and it remains uncertain whether markers with prognostic significance in adults also have predictive value in these patients. Fourteen cases of OGs in young patients (age, ≤ 25 years) who received a diagnosis over 7 years were selected (7 pediatric patients age ≤ 18 years and 7 young adults aged 19-25 years). The cases were evaluated for 1p/19q status, MGMT promoter methylation, p53 mutation, and IDH1 mutation. None of the pediatric cases showed 1p/19q deletion. In young adults, combined 1p/19q loss was observed in 57% and isolated 1p loss in 14% of cases. The majority of cases in both subgroups (71% in each) harbored MGMT gene promoter methylation. TP53 and IDH1 mutations were not seen in any of the cases in both the groups. To our knowledge, this is the first study to show that molecular profile of OGs in pediatric and young adult patients is distinct. Further large-scale studies are required to identify additional clinically relevant genetic alterations in this group of patients.

Fig. 1.

Hetrozygosity status of 1p chromosome, as determined by FISH). (A) A case showing 2 red (test: 1p36) and 2 green (control: 1q 25) signals, implying no 1p deletion. (B) A case showing 1 red (test) and 2 green (control) signals, implying 1p deletion.

Fig. 2.

Methylation status of the MGMT promoter, as determined by methylation-specific PCR assay. DNA from normal peripheral blood lymphocytes (PBL) was used as a control for the unmethylated MGMT promoter (U), enzymatically methylated lymphocytic DNA (SW48) served as a positive control for the methylated MGMT promoter (M), and water was used as a negative control for the PCR. A 100-bp marker ladder (L) was loaded to estimate molecular size. M: PCR product amplified by methylation-specific primers; U: PCR product amplified by unmethylated-specific primers; L: ladder; SW48: methylated control DNA; PBL: unmethylated control DNA. Samples 1, 2, 3, 5, 6, 7, 9, 11, 12, and 13 were methylated with presence of band in methylated “M” lane. Band in “U” lane is because of lymphocytes and normal tissue present with tumor tissue. Cases 4, 8, 10, and 14 were unmethylated with no band in “M” lane. In control samples, PBL had a band only in “U” lane, whereas SW48 had a band only in “M” lane.