TY - JOUR
T1 - Clinical next-generation sequencing reveals aggressive cancer biology in adolescent and young adult patients
AU - Subbiah, Vivek
AU - Bupathi, Manojkumar
AU - Kato, Shumei
AU - Livingston, Andrew
AU - Slopis, John
AU - Anderson, Pete M.
AU - Hong, David S.
N1 - Funding Information:
The University of Texas MD Anderson Cancer Center is supported in part by a Cancer Center Support Grant (CA016672) from the National Institutes of Health. Vivek Subbiah acknowledges support from the Shanon Wilkes Osteosarcoma Research fund. The authors wish to acknowledge the Jeanne F. Shelby Scholarship Fund for Investigational Cancer Therapeutics.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - AKT
KW - AYA
KW - Adolescents and young adults
KW - Cancer biology
KW - Next generation sequencing
KW - TP53
KW - mTOR
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U2 - 10.18632/oncoscience.176
DO - 10.18632/oncoscience.176
M3 - Article
C2 - 26328274
AN - SCOPUS:84958975436
SN - 2331-4737
VL - 2
SP - 646
EP - 652
JO - Oncoscience
JF - Oncoscience
IS - 7
ER -