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Espaço de publicação e discussão sobre oncologia. GBM IMMUNOTHERAPY ONCO-VIRUS ONCOLOGY CANCER CHEMOTHERAPY RADIOTHERAPY



Terça-feira, 23.06.15

Tumor profiling on 1245 gliomas and paired tumor study on 19 high grade gliomas.

Tumor profiling on 1245 gliomas and paired tumor study on 19 high grade gliomas.

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
Poster Session, Central Nervous System Tumors
Abstract Number: 

2058

Poster Board Number: 
Board #47
Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 2058)
Author(s): 
Joanne Xiu, David Spetzler, Ryan Bender, Anatole Ghazalpour, Zoran Gatalica, Sandeep K. Reddy, David Eric Piccioni, Jethro Lisien Hu, Michael J. Glantz, Santosh Kesari; Caris Life Sciences, Phoenix, AZ; Caris Life Sci, Paradise Valley, AZ; UC San Diego Moores Cancer Center, San Diego, CA; Cedars-Sinai, Los Angeles, CA; Penn State - Milton S Hershey Medcl Ctr, Hinsdale, MA; UC San Diego, La Jolla, CA

Abstract Disclosures

Abstract: 

Background: Gliomas are molecularly heterogeneous with genetic alterations driving the growth of recurrences different from the initial tumor. Previous reports showed molecular changes during progression of lower grade gliomas to GBM, driving tumor growth and treatment resistance; however changes during progression of high-grade gliomas have not been systematically reported. Methods: 1245 glioma tumors (934 GBM) were tested with multiple platforms including sequencing (SEQ), immunohistochemistry (IHC), fluorescent/chromogenic in-situ hybridization (FISH/CISH), fragment analysis (FA) and promoter methylation (Me) assay. Metachronous paired tumors from 19 patients (pts) were assessed for biomarker changes over time. Results: EGFRvIII was seen exclusively in GBM (16% of GBM) while amplification was more common in GBM than grade II-III tumors (56% vs. 20%, p < 0.001). MGMT Me was seen in 47% of all, and was more common in grade II-III (64% vs. 42%, p < 0.001). PD-L1 expression on tumor cells was seen in 27% and was more common in tumors without MGMT Me (36% vs. 18%, p = 0.01). PD-1 expression on tumor-infiltrating lymphocytes was seen in 48% and was higher in GBM than grade II-III(54% vs. 30%, p = 0.005). 38 of 48 sequenced genes had mutations, including BRCA1 (8%) and BRCA2 (6%). 1p19q co-deletion was seen in 26% of grade II-III and 2.9% of GBM. Paired tumors from 19 pts (18 GBM and 1 grade III in both samples) taken at an average of 469 days apart (91-1400) showed that 17 pairs (89%) had one or more biomarker changes over time. 3 of 13 (23%) pairs lost MGMT Me, potentially indicating acquired resistance to temozolomide. EGFR aberrations including amplification (N = 1), mutations on the extracellular (EGFRvIII, N = 1) and intracellular domains (T790M, N = 1; Exon 20 insertion N = 1) were acquired in 3 pairs. One pt, presenting with a PTEN mutation, acquired three additional mutations: cKIT (E583K), PTPN11 (A72T) and PIK3CA (D434N). Conclusions: Multiplatform tumor profiling on a large cohort of gliomas confirms tumor heterogeneity. Changes in MGMT Me and EGFR of potential therapeutic importance are frequently observed in high grade gliomas at the time of recurrence, suggesting the need for a re-biopsy for tumor profiling to direct the next line of therapy.

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por cyto às 17:04



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