Applicability of Routine Targeted Next-generation Sequencing to Estimate Tumor Mutational Burden (TMB) in Patients Treated with Immune Checkpoint Inhibitor Therapy

David J. Pinato, Heather Urus, Thomas Newsom-Davis, Persephone Du Parcq, Katherine Belessiotis, Leah Mapara, Nandita Gupta, Danielle Power, Justin Weir, Ching Ngar Wong, Ragu P. Ratnakumaran, Kathy Dominy, Jamshid Khorashad, Mark Bower

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

It remains unclear whether targeted next-generation sequencing (tNGS) conveys a reliable estimate of tumor mutational burden (TMB). We sequenced 79 archival samples of immune checkpoint inhibitors (ICPIs) recipients (57% lung cancer, 43% melanoma) using Ion Ampliseq Cancer Hotspot Panel. Employing multiple cutoff values, we verified that TMB by tNGS did not correlate with response or survival following ICPI. We found enrichment of ATM mutations in ICPI-refractory tumors (P=0.01) to correlate with worse survival (4.2 vs. 10 mo, P=0.03). Limited-coverage tNGS delivers an imprecise estimate of patients' TMB but may aid identification of candidate somatic variants of predictive/prognostic significance.

Lingua originaleInglese
pagine (da-a)53-56
Numero di pagine4
RivistaJournal of Immunotherapy
Volume43
Numero di pubblicazione2
DOI
Stato di pubblicazionePubblicato - 1 feb 2020
Pubblicato esternamente

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