TY - JOUR
T1 - Unique aberrations in intimal sarcoma identified by next-generation sequencing as potential therapy targets
AU - Roszik, Jason
AU - Khan, Abir
AU - Conley, Anthony P.
AU - Livingston, J. Andrew
AU - Groisberg, Roman
AU - Ravi, Vinod
AU - Pestana, Roberto Carmagnani
AU - Sen, Shiraj
AU - Subbiah, Vivek
N1 - Funding Information:
The University of Texas MD Anderson Cancer Center is supported by grant CA016672 from the National Institutes of Health. Acknowledgments: The authors would like to acknowledge the American Association for Cancer Research and its financial and material support in the development of the AACR Project GENIE registry, as well as members of the consortium for their commitment to data sharing. Interpretations are the responsibility of study authors.
Funding Information:
Funding: The University of Texas MD Anderson Cancer Center is supported by grant CA016672 from the National Institutes of Health.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/9
Y1 - 2019/9
N2 - Intimal sarcomas are rare and histologically heterogeneous tumors, commonly arising from the pulmonary arteries. They have remained challenging to treat. Few studies in the literature study the genomics of this cancer. Identifying targetable alterations is an important step in advancing the treatment of intimal sarcomas. Using data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (AACR GENIE) database, we cataloged genetic alterations and assessed their clinical utility from thirteen patients with intimal sarcoma. Notable copy number alterations included amplification in MDM2, CDK4, PDGFRA, and NOTCH2, as well as copy number losses in CDKN2A and CDKN2B. Actionable alterations included mutations in ATM/ATR, PTCH1, and PDGFRB. Moreover, genomic rearrangement events, specifically PDE4DIP-NOTCH2 and MRPS30-ARID2 fusions were identified. Co-occurring alterations included a NOTCH2 copy number gain in the PDE4DIP-NOTCH2 fusion positive tumor and PDGFRB mutations in both fusion-positive cases. Our study suggests that PDGFRB may be relevant in the tumorigenesis process. Including genomic profiling in the management of intimal sarcoma and potential enrollment in targeted therapy trials is warranted.
AB - Intimal sarcomas are rare and histologically heterogeneous tumors, commonly arising from the pulmonary arteries. They have remained challenging to treat. Few studies in the literature study the genomics of this cancer. Identifying targetable alterations is an important step in advancing the treatment of intimal sarcomas. Using data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (AACR GENIE) database, we cataloged genetic alterations and assessed their clinical utility from thirteen patients with intimal sarcoma. Notable copy number alterations included amplification in MDM2, CDK4, PDGFRA, and NOTCH2, as well as copy number losses in CDKN2A and CDKN2B. Actionable alterations included mutations in ATM/ATR, PTCH1, and PDGFRB. Moreover, genomic rearrangement events, specifically PDE4DIP-NOTCH2 and MRPS30-ARID2 fusions were identified. Co-occurring alterations included a NOTCH2 copy number gain in the PDE4DIP-NOTCH2 fusion positive tumor and PDGFRB mutations in both fusion-positive cases. Our study suggests that PDGFRB may be relevant in the tumorigenesis process. Including genomic profiling in the management of intimal sarcoma and potential enrollment in targeted therapy trials is warranted.
KW - AACR GENIE
KW - Copy number alteration
KW - Gene fusion
KW - Intimal sarcoma
KW - Next-generation sequencing
KW - Somatic mutation
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U2 - 10.3390/cancers11091283
DO - 10.3390/cancers11091283
M3 - Article
C2 - 31480474
AN - SCOPUS:85073363913
SN - 2072-6694
VL - 11
JO - Cancers
JF - Cancers
IS - 9
M1 - 1283
ER -