TY - JOUR
T1 - Comprehensive genomic profiling of esthesioneuroblastoma reveals additional treatment options
AU - Gay, Laurie M.
AU - Kim, Sungeun
AU - Fedorchak, Kyle
AU - Kundranda, Madappa
AU - Odia, Yazmin
AU - Nangia, Chaitali
AU - Battiste, James
AU - Colon-Otero, Gerardo
AU - Powell, Steven
AU - Russell, Jeffery
AU - Elvin, Julia A.
AU - Vergilio, Jo Anne
AU - Suh, James
AU - Ali, Siraj M.
AU - Stephens, Philip J.
AU - Miller, Vincent A.
AU - Ross, Jeffrey S.
N1 - Publisher Copyright:
© AlphaMed Press.
PY - 2017/7
Y1 - 2017/7
N2 - Background. Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit. Materials and Methods. We queried whether comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover genomic alterations (GA) that could identify potential targeted therapies for these patients. CGP was performed on formalin-fixed, paraffin-embedded sections from 41 consecutive clinical cases of ENBs using a hybrid-capture, adaptor ligation based next-generation sequencing assay to a mean coverage depth of 593X.The results were analyzed for base substitutions, insertions and deletions, select rearrangements, and copy number changes (amplifications and homozygous deletions). Results. Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in clinical trials. A total of 28 ENBs harbored GA, with a mean of 1.5 GA per sample. Approximately half of the ENBs (21, 51%) featured at least one CRGA, with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), with GA in PIK3CA, NF1, CDKN2A, and CDKN2C occurring in 7% of samples. Conclusion. We report comprehensive genomic profiles for 41 ENB tumors. CGP revealed potential new therapeutic targets, including targetable GA in the mTOR, CDK and growth factor signaling pathways, highlighting the clinical value of genomic profiling in ENB.
AB - Background. Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit. Materials and Methods. We queried whether comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover genomic alterations (GA) that could identify potential targeted therapies for these patients. CGP was performed on formalin-fixed, paraffin-embedded sections from 41 consecutive clinical cases of ENBs using a hybrid-capture, adaptor ligation based next-generation sequencing assay to a mean coverage depth of 593X.The results were analyzed for base substitutions, insertions and deletions, select rearrangements, and copy number changes (amplifications and homozygous deletions). Results. Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in clinical trials. A total of 28 ENBs harbored GA, with a mean of 1.5 GA per sample. Approximately half of the ENBs (21, 51%) featured at least one CRGA, with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), with GA in PIK3CA, NF1, CDKN2A, and CDKN2C occurring in 7% of samples. Conclusion. We report comprehensive genomic profiles for 41 ENB tumors. CGP revealed potential new therapeutic targets, including targetable GA in the mTOR, CDK and growth factor signaling pathways, highlighting the clinical value of genomic profiling in ENB.
KW - Comprehensive genomic profiling
KW - Esthesioneuroblastoma
KW - Everolimus
KW - Next-generation sequencing
KW - Pazopanib
KW - Sunitinib
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U2 - 10.1634/theoncologist.2016-0287
DO - 10.1634/theoncologist.2016-0287
M3 - Article
C2 - 28495808
AN - SCOPUS:85024126493
SN - 1083-7159
VL - 22
SP - 834
EP - 842
JO - Oncologist
JF - Oncologist
IS - 7
ER -