Abstract 5080: Clinical next generation sequencing of adolescents and young adult (AYA) patients with cancer reveals aggressive biology: A preliminary report from a major cancer center
Authors: Bupathi Manojkumar , Hong David S. , Anderson Pete M. , Subbiah Vivek 
Published: May 2015

Introduction: The survival of adolescents and young adults (AYA), (age 15-39 years), with cancer are worse when compared to younger (&lt;15 yr) and older (&gt; 45 yr) patients across all cancer registries (USA, UK and Australia). One of the reasons cited for the inferior outcomes is the aggressive biology of cancers (both adult and pediatric type) that arise in this population. Clinical next generation sequencing (NGS) may unravel some of the molecular alterations and diverse biology.

Methods: A methodical chart review of AYA patients who were referred to the Department of Investigational Cancer Therapeutics (A Phase I Program) from July 2012 to May 2013 was performed. All patients had clinical NGS testing of archival tumor tissue by FoundationOne platform, a CLIA certified testing for identification of targetable molecular alterations.

Results: Among the 27 patients analyzed (14 F: 13 M), eight were adult type cancers, twelve were pediatric type cancers and seven were orphan cancers. Unique aberrations were identified in all types of cancers that have been hitherto unreported in the COSMIC database. Of note, TP53, NKX2-1, KRAS, CDKN2A, MDM4, MCL1, MYC, BCL2L2, and RB1 were the aberrations seen across all tumor types in this population. TP53 aberrations were seen in five patients, three patients harbored MYC, MCL1, and CDKN2A aberrations and two patients had alterations in NKX2-1, KRAS, MDM4, BCL2L2, and RB1. The tumor types included pediatric type tumors like osteosarcoma (N=5), medulloblastoma (N=2), alveolar rhabomyosarcoma (N=3), neuroblastoma (N=1), Wilms tumor (N=1); adult type tumors like non-small cell lung cancer (N=1), colorectal cancer (N=1), nasopharyngeal carcinoma (N=2); triple negative breast cancer (N=1), gastric adenocarcinoma (N=1); orphan cancers like, fibrolamellar hepatocellular carcinoma (N=1), junvenile hyalinized fibromatosis (N=1), renal medullary carcinoma(N=2), MPNST (N=1), neurofibromatosis type 2 ( N=1), small cell sarcoma (N=1), gastrointestinal stromal tumor (GIST)(N=1), and neuroendocrine carcinoma of lung (N=1). Several patients had multiple aberrations viz, the wild type GIST patient harbored 5 alterations (MDM4, MCL1, KIT, AKT3, PDGRFA).

Conclusions: A preliminary report of NGS sequencing in AYA reveals diverse and unique aberrations. AYA patients have physiological and pharmacological differences in addition to genomic mutations compared to younger and older patients in regards to cancer treatment. Further molecular profiling and deeper understanding of the biology of these unique aberrations are warranted.

Citation Format: Manojkumar Bupathi, David S. Hong, Pete M. Anderson, Vivek Subbiah. Clinical next generation sequencing of adolescents and young adult (AYA) patients with cancer reveals aggressive biology: A preliminary report from a major cancer center. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5080. doi:10.1158/1538-7445.AM2014-5080