Abstract
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. 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. 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). 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.
Highlights
Over the past few decades, treatment for aggressive cancers in both adult and pediatric patients has substantially improved, increasing survival rates for these groups [1]
Increasing awareness has led to interest in defining the psychosocial and host-related factors that contribute to the discrepant and poor outcomes observed in AYA patients
We report a preliminary analysis of next-generation sequencing (NGS) profiles of all AYA patients referred to the Center for Targeted Therapy, a phase I clinical trials program at our institution
Summary
Over the past few decades, treatment for aggressive cancers in both adult and pediatric patients has substantially improved, increasing survival rates for these groups [1]. Multiple authors have examined the effects of psychosocial factors, poor medication compliance, and under-insurance on outcomes [2,5]. These psychosocial causes are compounded by host-related factors such as decreased tolerance to intensive chemotherapy regimens, comorbidities, and unique pharmacodynamics that accompany puberty and are a part of the normal aging process. 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. Aberrations in TP53, NKX2-1, KRAS, CDKN2A, MDM4, MCL1, MYC, BCL2L2, and RB1 were demonstrated across all tumor types. Several patients had multiple aberrations; a patient with wild-type gastrointestinal stromal tumor harbored five alterations (MDM4, MCL1, KIT, AKT3, and PDGRFA). Further molecular profiling and a deeper understanding of the biology of these unique aberrations are warranted and may lead to targeted therapeutic interventions
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