101. Molecular Characterization of IDHWild-type Diffuse Astrocytomas: The Potential of cIMPACT-NOW Guidelines
- Author
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Kumari, Kalpana, Dandapath, Iman, Singh, Jyotsna, Rai, Hitesh I.S., Kaur, Kavneet, Jha, Prerana, Malik, Nargis, Chosdol, Kunzang, Mallick, Supriya, Garg, Ajay, Suri, Ashish, Sharma, Mehar C., Sarkar, Chitra, and Suri, Vaishali
- Abstract
IDHwild-type (wt) grade 2/3 astrocytomas are a heterogenous group of tumors with disparate clinical and molecular profiles. cIMPACT-NOW recommendations incorporated in the new 2021 World Health Organization (WHO) Classification of Central Nervous System (CNS) Tumors urge minimal molecular criteria to identify a subset that has an aggressive clinical course similar to IDH-wt glioblastomas (GBMs). This paper describes the use of a panel of molecular markers to reclassify IDH-wt grade 2/3 diffuse astrocytic gliomas (DAGs) and study median overall survival concerning for to IDH-wt GBMs in the Indian cohort. IDH-wt astrocytic gliomas (grades 2, 3, and 4) confirmed by IDHR132H immunohistochemistry and IDH1/2gene sequencing, 1p/19q non–codeleted with no H3F3Amutations were included. TERTpromoter mutation by Sanger sequencing, epidermal growth factor receptor amplification, and whole chromosome 7 gain and chromosome 10 loss by fluorescence in situ hybridization was assessed and findings correlated with clinical and demographic profiles. The molecular profile of 53 IDH-wt DAGs (grade 2: 31, grade 3: 22) was analyzed. Eleven cases (grade 2: 8, grade 3: 3) (20.75%) were reclassified as IDH-wt GBMs, WHO grade 4 (TERTpromoter mutation in 17%, epidermal growth factor receptor amplification in 5.5%, and whole chromosome 7 gain and chromosome 10 loss in 2%). Molecular GBMs were predominantly frontal (54.5%) with a mean age of 36 years and median overall survival equivalent to IDH-wt GBMs (18 vs. 19 mo; P=0.235). Among grade 2/3 DAGs not harboring these alterations, significantly better survival was observed for grade 2 versus grade 3 DAGs (25 vs. 16 mo; P=0.002). Through the incorporation of a panel of molecular markers, a subset of IDH-wt grade 2 DAGs can be stratified into molecular grade 4 tumors with prognostic and therapeutic implications. However, IDH-wt grade 3 DAGs behave like GBMs irrespective of molecular profile.
- Published
- 2022
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