Fusion gene profile of biphenotypic sinonasal sarcoma: An analysis of 44 cases

Karen J. Fritchie, Long Jin, Xiaoke Wang, Rondell Graham, Michael Torbenson, Jean E. Lewis, Michael Rivera, Joaquin J. Garcia, David J. Schembri-Wismayer, Jennifer J Westendorf, Margaret M. Chou, Jie Dong, Andre M. Oliveira

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Aims: Biphenotypic sinonasal sarcoma (SNS) is a locally aggressive tumour that occurs in the sinonasal region. PAX3-MAML3 has recently been identified as a recurrent fusion gene event in this entity; however, a subset of tumours harbour alternative PAX3 rearrangement without the involvement of MAML3. In this study we sought to characterize the molecular profile of a large series of cases, with a special emphasis on tumours with alternative fusions. Methods and results: Forty-four examples of SNS were screened by fluorescence in-situ hybridization and reverse transcription polymerase chain reaction to better characterize its molecular profile and identify potential novel fusion genes. Twenty-four were positive for PAX3-MAML3 (55%), 15 showed rearrangements of PAX3 without MAML3 involvement (34%), one showed rearrangement of MAML3 without PAX3 involvement, and four were negative for the involvement of either gene (9%). Among 15 cases with PAX3 involvement only, three were found to harbour PAX3-FOXO1. Two of these cases arose in the nasal cavities of female patients (aged 31 and 47 years), and one showed bilateral involvement of the nasal cavities of a 35-year-old male. A fourth case involved the skull base of a 47-year-old male, and was positive for PAX3-NCOA1. Patients with fusion-negative tumours were slightly older. Conclusion: More than half of the SNSs in this series were positive for PAX3-MAML3. However, a subset of tumours may harbour alternative PAX3 fusion genes or show no involvement of PAX3. Except for a possible weak association between age and molecular profile, the overall morphological and immunophenotypic features of all cases seem to be similar. Because of the rarity of these tumours, the impact of the molecular profile on the clinical course of these tumours remains to be determined.

Original languageEnglish (US)
JournalHistopathology
DOIs
StateAccepted/In press - 2016

Fingerprint

Gene Fusion
Sarcoma
Neoplasms
Nasal Cavity
Skull Base
Fluorescence In Situ Hybridization
Reverse Transcription
Polymerase Chain Reaction
Genes

Keywords

  • MAML3
  • NCOA1
  • PAX3
  • FOXO1
  • Sinonasal sarcoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Fusion gene profile of biphenotypic sinonasal sarcoma : An analysis of 44 cases. / Fritchie, Karen J.; Jin, Long; Wang, Xiaoke; Graham, Rondell; Torbenson, Michael; Lewis, Jean E.; Rivera, Michael; Garcia, Joaquin J.; Schembri-Wismayer, David J.; Westendorf, Jennifer J; Chou, Margaret M.; Dong, Jie; Oliveira, Andre M.

In: Histopathology, 2016.

Research output: Contribution to journalArticle

Fritchie, KJ, Jin, L, Wang, X, Graham, R, Torbenson, M, Lewis, JE, Rivera, M, Garcia, JJ, Schembri-Wismayer, DJ, Westendorf, JJ, Chou, MM, Dong, J & Oliveira, AM 2016, 'Fusion gene profile of biphenotypic sinonasal sarcoma: An analysis of 44 cases', Histopathology. https://doi.org/10.1111/his.13045
Fritchie, Karen J. ; Jin, Long ; Wang, Xiaoke ; Graham, Rondell ; Torbenson, Michael ; Lewis, Jean E. ; Rivera, Michael ; Garcia, Joaquin J. ; Schembri-Wismayer, David J. ; Westendorf, Jennifer J ; Chou, Margaret M. ; Dong, Jie ; Oliveira, Andre M. / Fusion gene profile of biphenotypic sinonasal sarcoma : An analysis of 44 cases. In: Histopathology. 2016.
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title = "Fusion gene profile of biphenotypic sinonasal sarcoma: An analysis of 44 cases",
abstract = "Aims: Biphenotypic sinonasal sarcoma (SNS) is a locally aggressive tumour that occurs in the sinonasal region. PAX3-MAML3 has recently been identified as a recurrent fusion gene event in this entity; however, a subset of tumours harbour alternative PAX3 rearrangement without the involvement of MAML3. In this study we sought to characterize the molecular profile of a large series of cases, with a special emphasis on tumours with alternative fusions. Methods and results: Forty-four examples of SNS were screened by fluorescence in-situ hybridization and reverse transcription polymerase chain reaction to better characterize its molecular profile and identify potential novel fusion genes. Twenty-four were positive for PAX3-MAML3 (55{\%}), 15 showed rearrangements of PAX3 without MAML3 involvement (34{\%}), one showed rearrangement of MAML3 without PAX3 involvement, and four were negative for the involvement of either gene (9{\%}). Among 15 cases with PAX3 involvement only, three were found to harbour PAX3-FOXO1. Two of these cases arose in the nasal cavities of female patients (aged 31 and 47 years), and one showed bilateral involvement of the nasal cavities of a 35-year-old male. A fourth case involved the skull base of a 47-year-old male, and was positive for PAX3-NCOA1. Patients with fusion-negative tumours were slightly older. Conclusion: More than half of the SNSs in this series were positive for PAX3-MAML3. However, a subset of tumours may harbour alternative PAX3 fusion genes or show no involvement of PAX3. Except for a possible weak association between age and molecular profile, the overall morphological and immunophenotypic features of all cases seem to be similar. Because of the rarity of these tumours, the impact of the molecular profile on the clinical course of these tumours remains to be determined.",
keywords = "MAML3, NCOA1, PAX3, FOXO1, Sinonasal sarcoma",
author = "Fritchie, {Karen J.} and Long Jin and Xiaoke Wang and Rondell Graham and Michael Torbenson and Lewis, {Jean E.} and Michael Rivera and Garcia, {Joaquin J.} and Schembri-Wismayer, {David J.} and Westendorf, {Jennifer J} and Chou, {Margaret M.} and Jie Dong and Oliveira, {Andre M.}",
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T1 - Fusion gene profile of biphenotypic sinonasal sarcoma

T2 - An analysis of 44 cases

AU - Fritchie, Karen J.

AU - Jin, Long

AU - Wang, Xiaoke

AU - Graham, Rondell

AU - Torbenson, Michael

AU - Lewis, Jean E.

AU - Rivera, Michael

AU - Garcia, Joaquin J.

AU - Schembri-Wismayer, David J.

AU - Westendorf, Jennifer J

AU - Chou, Margaret M.

AU - Dong, Jie

AU - Oliveira, Andre M.

PY - 2016

Y1 - 2016

N2 - Aims: Biphenotypic sinonasal sarcoma (SNS) is a locally aggressive tumour that occurs in the sinonasal region. PAX3-MAML3 has recently been identified as a recurrent fusion gene event in this entity; however, a subset of tumours harbour alternative PAX3 rearrangement without the involvement of MAML3. In this study we sought to characterize the molecular profile of a large series of cases, with a special emphasis on tumours with alternative fusions. Methods and results: Forty-four examples of SNS were screened by fluorescence in-situ hybridization and reverse transcription polymerase chain reaction to better characterize its molecular profile and identify potential novel fusion genes. Twenty-four were positive for PAX3-MAML3 (55%), 15 showed rearrangements of PAX3 without MAML3 involvement (34%), one showed rearrangement of MAML3 without PAX3 involvement, and four were negative for the involvement of either gene (9%). Among 15 cases with PAX3 involvement only, three were found to harbour PAX3-FOXO1. Two of these cases arose in the nasal cavities of female patients (aged 31 and 47 years), and one showed bilateral involvement of the nasal cavities of a 35-year-old male. A fourth case involved the skull base of a 47-year-old male, and was positive for PAX3-NCOA1. Patients with fusion-negative tumours were slightly older. Conclusion: More than half of the SNSs in this series were positive for PAX3-MAML3. However, a subset of tumours may harbour alternative PAX3 fusion genes or show no involvement of PAX3. Except for a possible weak association between age and molecular profile, the overall morphological and immunophenotypic features of all cases seem to be similar. Because of the rarity of these tumours, the impact of the molecular profile on the clinical course of these tumours remains to be determined.

AB - Aims: Biphenotypic sinonasal sarcoma (SNS) is a locally aggressive tumour that occurs in the sinonasal region. PAX3-MAML3 has recently been identified as a recurrent fusion gene event in this entity; however, a subset of tumours harbour alternative PAX3 rearrangement without the involvement of MAML3. In this study we sought to characterize the molecular profile of a large series of cases, with a special emphasis on tumours with alternative fusions. Methods and results: Forty-four examples of SNS were screened by fluorescence in-situ hybridization and reverse transcription polymerase chain reaction to better characterize its molecular profile and identify potential novel fusion genes. Twenty-four were positive for PAX3-MAML3 (55%), 15 showed rearrangements of PAX3 without MAML3 involvement (34%), one showed rearrangement of MAML3 without PAX3 involvement, and four were negative for the involvement of either gene (9%). Among 15 cases with PAX3 involvement only, three were found to harbour PAX3-FOXO1. Two of these cases arose in the nasal cavities of female patients (aged 31 and 47 years), and one showed bilateral involvement of the nasal cavities of a 35-year-old male. A fourth case involved the skull base of a 47-year-old male, and was positive for PAX3-NCOA1. Patients with fusion-negative tumours were slightly older. Conclusion: More than half of the SNSs in this series were positive for PAX3-MAML3. However, a subset of tumours may harbour alternative PAX3 fusion genes or show no involvement of PAX3. Except for a possible weak association between age and molecular profile, the overall morphological and immunophenotypic features of all cases seem to be similar. Because of the rarity of these tumours, the impact of the molecular profile on the clinical course of these tumours remains to be determined.

KW - MAML3

KW - NCOA1

KW - PAX3

KW - FOXO1

KW - Sinonasal sarcoma

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