Clinical next-generation sequencing reveals aggressive cancer biology in adolescent and young adult patients
Vivek Subbiah1, Manojkumar Bupathi1, Shumei Kato1, Andrew Livingston2,John Slopis3, Pete M. Anderson4, David S. Hong1
1 Department of Phase I Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas
2 Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
3 Department of Neuro-oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
4 Pediatric Hematology Oncology and Blood and Marrow Transplantation, Cleveland Clinic Foundation, Cleveland, OH
Correspondence:
Vivek Subbiah, email:
Keywords: next generation sequencing, adolescents and young adults, cancer biology, AYA, mTOR, AKT, TP53
Received: June 23, 2015 Accepted: July 1, 2015 Published: July 8, 2015
Abstract
Background:The aggressive biology of cancers arising in adolescent and young adult (AYA; ages 15–39 years) patients is thought to contribute to poor survival outcomes. Methods: We used clinical next-generation sequencing (NGS) results to examine the molecular alterations and diverse biology of cancer in AYA patients referred to the Phase 1 program at UT MD Anderson Cancer Center. Results: Among the 28 patients analyzed (14 female and 14 male), 12 had pediatric-type cancers, six had adult-type cancers, and ten had orphan cancers. Unique, hitherto unreported aberrations were identified in all types of cancers. Aberrations in TP53, NKX2-1, KRAS, CDKN2A, MDM4, MCL1, MYC, BCL2L2, andRB1 were demonstrated across all tumor types. Five patients harbored TP53 aberrations; three patients harbored MYC, MCL1, andCDKN2A aberrations;andtwo patients harbored NKX2-1, KRAS, MDM4, BCL2L2, andRB1 alterations. Several patients had multiple aberrations; a patient with wild-type gastrointestinal stromal tumor harbored five alterations (MDM4, MCL1, KIT, AKT3, andPDGRFA). Conclusions: This preliminary report of NGS of cancer in AYA patients reveals diverse and unique aberrations. Further molecular profiling and a deeper understanding of the biology of these unique aberrations are warranted and may lead to targeted therapeutic interventions.
