83. Cytogenetic and molecular characterization of IDH-mutant adult-type diffuse gliomas with near-total 1p/19q co-deletions

Aly Abdelkareem

Cinthya Zepeda Mendoza

I am a Senior Associate Consultant at the Division of Hematopathology and Laboratory Genetics and Genomics from the Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, MN. I received my Laboratory Genetics and Genomics (LGG) certification from the American Board of Medical Genetics and Genomics in 2021 and was formerly a Medical Director at ARUP Laboratories and Assistant Professor of Pathology at the University of Utah from 2020 to 2022.

My primary areas of career expertise and interest have been in pediatric hematopathology (primarily B lymphoblastic leukemia) and the study of complex chromosome rearrangements in hematological malignancies and congenital disorders. At Mayo Clinic, these characterizations have heavily focused on the utilization of next-generation sequencing (NGS), genomic microarray, and classic cytogenetic techniques such as FISH and chromosome analysis. Additional interests and work include minimal/measurable residual disease testing; the study of molecular signatures of adult diffuse gliomas; and the initial development and validation of clinical germline whole genome sequencing.

I am highly engaged in teaching Cytogenetics to rotating residents and fellows from various specialties, and I am an active participant in several molecular pathology and human genetics and genomics national committees. I am currently serving as the Chair of the Diversity, Equity, and Inclusion Committee from the American College of Medical Genetics and Genomics and a member of the Communications Committee from the Cancer Genomics Consortium.



Cinthya Zepeda Mendoza, Thomas Kollmeyer, Corinne Praska, Katherine Geiersbach, William Sukov, Patricia Greipp, Aditya Raghunathan, Caterina Giannini, Robert Jenkins, Cristiane Ida

Mayo Clinic, Rochester, MN, United States

Whole-arm 1p/19q co-deletion is a diagnostic criterion for oligodendroglioma, IDH-mutant and 1p/19q-codeleted. The significance of near-total co-deletions of 1p and 19q arms ((≥75%) is unclear. We cytogenetically and molecularly characterized 15 IDH-mutant adult-type diffuse gliomas with near-total 1p/19q co-deletions encountered in routine testing by a single reference laboratory using OncoScanTM CNV Plus and targeted neuro-oncology NGS panels (2017-2021). Median age at surgery was 51 years (range 34-74). Most tumors reportedly represented primary resections (13/15; 87%) with high-grade histological features (8/15; 53%). Of the 15 cases, four (27%) had near-total 1p with near-total 19q codeletion, four (27%) had near-total 1p deletion (including one with terminal copy-neutral loss of heterozygosity [cnLOH]) with 19q whole-arm deletion, and seven (47%) had whole-arm 1p deletion with near-total 19q deletion (including one with terminal cnLOH). Except for 9p allelic imbalance including CDKN2A/B in 9/15 (60%) cases (six with cnLOH, three with heterozygous deletion), genomes were otherwise stable. All cases were IDH1 mutant (13 with R132H, one with R132G, and one with R132S) and 14/15 (93%) cases were TERT promoter mutant (9 with C228T, 5 with C250T). Additional recurrent mutations involved CIC (9/15; 60%), FUBP1 (6/15; 40%), PIK3CA (3/15; 20%), PIK3R1 (3/15; 20%) and NOTCH1 (2/15; 13%). The single case without TERT promoter mutation harbored a CIC mutation. Comprehensive cytogenetic and molecular profiling of IDH-mutant adult-type diffuse gliomas with near-total 1p/19q co-deletions shows features in keeping with oligodendroglioma, IDH-mutant and 1p/19q-codeleted, suggesting that near-total 1p/19q co-deletions may be diagnostically equivalent to whole-arm 1p/19q co-deletion in this context.