Integrated genomic characterization of oral carcinomas in post-hematopoietic stem cell transplantation survivors

Publication date: June 2018
Source:Oral Oncology, Volume 81
Author(s): Glenn J. Hanna, Eric R. Kofman, Muhammad Ali Shazib, Sook-bin Woo, Brendan Reardon, Nathaniel S. Treister, Robert I. Haddad, Corey S. Cutler, Joseph H. Antin, Eliezer M. Van Allen, Ravindra Uppaluri, Robert J. Soiffer
ObjectivesSecondary oral squamous cell carcinoma (OSCC) is a late complication in allogeneic hematopoietic stem cell transplantation (HSCT) patients, but little is known about long-term outcomes and prognostication. Additionally, molecular alterations and immunologic insights unique to this disease remain largely unexplored.MethodsWe present a cohort of 31 patients with post-HSCT OSCC and reported on clinicopathologic predictors of survival. Whole-exome sequencing was performed on 6 (19%) matched pairs of peripheral blood (post-conditioning, pre-HSCT) and tumor samples. The entire cohort had archival tumor available for immunoprofiling with PD-1/L1 immunohistochemistry.ResultsFive-year overall survival (OS) was 57% (95% CI: 46.1–69.8) with a median disease-free survival (DFS) of 13.3 months. Advanced initial staging, a buccal or oral tongue subsite, chronic oral graft-versus-host disease (GVHD) and smoking all negatively impacted survival. High tumor mutational burden (TMB) (median 11.3 vs. 5.0) and unique mutational signatures were noted between unrelated and related donor groups – with a strong correlation between infiltrating PD-1+ lymphocytes and TMB (R = 0.98, p < 0.01). Some differences were observed when comparing commonly mutated genes among our cohort and TCGA, with a predominance of TP53 events.ConclusionSurvival outcomes appear similar in HSCT survivors with OSCC compared with non-HSCT OSCC populations. We identified somatic alterations in genes with therapeutic potential unique to this subpopulation of oral cancers.



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