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Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options.
Oncologist 2017; 22(7):834-842O

Abstract

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.

IMPLICATIONS FOR PRACTICE

Comprehensive genomic profiling of 41 relapsed or refractory ENBs reveals recurrent alterations or classes of mutation, including amplification of tyrosine kinases encoded on chromosome 5q and mutations affecting genes in the mTOR/PI3K pathway. Approximately half of the ENBs (21, 51%) featured at least one clinically relevant genomic alteration (CRGA), with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), and alterations in PIK3CA, NF1, CDKN2A, or CDKN2C were identified in 7% of samples. Responses to treatment with the kinase inhibitors sunitinib, everolimus, and pazopanib are presented in conjunction with tumor genomics.

Authors+Show Affiliations

Foundation Medicine, Inc., Cambridge, Massachusetts, USA lgay@foundationmedicine.com.Department of Pathology, Albany Medical College, Albany, New York, USA.Foundation Medicine, Inc., Cambridge, Massachusetts, USA.Department of Medical Oncology, Banner MD Anderson Cancer Center, Gilbert, Arizona, USA.Department of Neurology, Columbia University - NY Presbyterian Medical Center, New York, New York, USA. Department of Neuro-Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida, USA.Chao Family Comprehensive Cancer Center, UC Irvine, Irvine, California, USA.Department of Neurology, Stephenson Cancer Center at Oklahoma University, Oklahoma City, Oklahoma, USA.Department of Oncology, Mayo Clinic, Jacksonville, Florida, USA.Sanford Health, Sioux Falls, South Dakota, USA.Department of Medical Oncology, Moffitt Cancer Center, Tampa, Florida, USA.Foundation Medicine, Inc., Cambridge, Massachusetts, USA.Foundation Medicine, Inc., Cambridge, Massachusetts, USA.Foundation Medicine, Inc., Cambridge, Massachusetts, USA.Foundation Medicine, Inc., Cambridge, Massachusetts, USA.Foundation Medicine, Inc., Cambridge, Massachusetts, USA.Foundation Medicine, Inc., Cambridge, Massachusetts, USA.Foundation Medicine, Inc., Cambridge, Massachusetts, USA. Department of Pathology, Albany Medical College, Albany, New York, USA.

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

28495808

Citation

Gay, Laurie M., et al. "Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options." The Oncologist, vol. 22, no. 7, 2017, pp. 834-842.
Gay LM, Kim S, Fedorchak K, et al. Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options. Oncologist. 2017;22(7):834-842.
Gay, L. M., Kim, S., Fedorchak, K., Kundranda, M., Odia, Y., Nangia, C., ... Ross, J. S. (2017). Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options. The Oncologist, 22(7), pp. 834-842. doi:10.1634/theoncologist.2016-0287.
Gay LM, et al. Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options. Oncologist. 2017;22(7):834-842. PubMed PMID: 28495808.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2017/05/11/ PY - 2016/07/20/received PY - 2017/02/06/accepted PY - 2017/5/13/pubmed PY - 2018/3/31/medline PY - 2017/5/13/entrez KW - Comprehensive genomic profiling KW - Esthesioneuroblastoma KW - Everolimus KW - Next‐generation sequencing KW - Pazopanib KW - Sunitinib SP - 834 EP - 842 JF - The oncologist JO - Oncologist VL - 22 IS - 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. IMPLICATIONS FOR PRACTICE: Comprehensive genomic profiling of 41 relapsed or refractory ENBs reveals recurrent alterations or classes of mutation, including amplification of tyrosine kinases encoded on chromosome 5q and mutations affecting genes in the mTOR/PI3K pathway. Approximately half of the ENBs (21, 51%) featured at least one clinically relevant genomic alteration (CRGA), with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), and alterations in PIK3CA, NF1, CDKN2A, or CDKN2C were identified in 7% of samples. Responses to treatment with the kinase inhibitors sunitinib, everolimus, and pazopanib are presented in conjunction with tumor genomics. SN - 1549-490X UR - https://www.unboundmedicine.com/medline/citation/28495808/Comprehensive_Genomic_Profiling_of_Esthesioneuroblastoma_Reveals_Additional_Treatment_Options_ L2 - https://doi.org/10.1634/theoncologist.2016-0287 DB - PRIME DP - Unbound Medicine ER -