Clinical next-generation sequencing reveals aggressive cancer biology in adolescent and young adult patients.
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, and RB1 were demonstrated across all tumor types. Five patients harbored TP53 aberrations; three patients harbored MYC, MCL1, and CDKN2A aberrations; and two patients harbored NKX2-1, KRAS, MDM4, BCL2L2, and RB1 alterations. Several patients had multiple aberrations; a patient with wild-type gastrointestinal stromal tumor harbored five alterations (MDM4, MCL1, KIT, AKT3, and PDGRFA).


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.
Department of Phase I Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Vivek
V
Subbiah
Department of Phase I Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Manojkumar
M
Bupathi
Department of Phase I Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Shumei
S
Kato
Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Andrew
A
Livingston
Department of Neuro-oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
John
J
Slopis
Pediatric Hematology Oncology and Blood and Marrow Transplantation, Cleveland Clinic Foundation, Cleveland, OH, USA.
Pete M
PM
Anderson
Department of Phase I Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
David S
DS
Hong
AKT; AYA; TP53; adolescents and young adults; cancer biology; mTOR; next generation sequencing