TY - JOUR
T1 - Targeted next generation sequencing of well-differentiated/ dedifferentiated liposarcoma reveals novel gene amplifications and mutations
AU - Somaiah, Neeta
AU - Beird, Hannah C.
AU - Barbo, Andrea
AU - Song, Juhee
AU - Mills Shaw, Kenna R.
AU - Wang, Wei Lien
AU - Eterovic, Karina
AU - Chen, Ken
AU - Lazar, Alexander
AU - Conley, Anthony P.
AU - Ravi, Vinod
AU - Hwu, Patrick
AU - Futreal, Andrew
AU - Simon, George
AU - Meric-Bernstam, Funda
AU - Hong, David
N1 - Publisher Copyright:
© Somaiah et al.
PY - 2018/4/13
Y1 - 2018/4/13
N2 - Well-differentiated/dedifferentiated liposarcoma is a common soft tissue sarcoma with approximately 1500 new cases per year. Surgery is the mainstay of treatment but recurrences are frequent and systemic options are limited. 'Tumor genotyping' is becoming more common in clinical practice as it offers the hope of personalized targeted therapy. We wanted to evaluate the results and the clinical utility of available nextgeneration sequencing panels in WD/DD liposarcoma. Patients who had their tumor sequenced by either FoundationOne (n = 13) or the institutional T200/T200.1 panels (n = 7) were included in this study. Significant copy number alterations were identified, but mutations were infrequent. Out of the 27 mutations detected in 7 samples, 8 (CTNNB1, MECOM, ZNF536, EGFR, EML4, CSMD3, PBRM1, PPP1R3A) were identified as deleterious (on Condel, PolyPhen and SIFT) and a truncating mutation was found in NF2. Of these, EGFR and NF2 are potential driver mutations and have not been reported previously in liposarcoma. MDM2 and CDK4 amplification was universally present in all the tested samples and multiple other recurrent genes with high amplification or high deletion were detected. Many of these targets are potentially actionable. Eight patients went on to receive an MDM2 inhibitor with a median time to progression of 23 months (95% CI: 10-83 months).
AB - Well-differentiated/dedifferentiated liposarcoma is a common soft tissue sarcoma with approximately 1500 new cases per year. Surgery is the mainstay of treatment but recurrences are frequent and systemic options are limited. 'Tumor genotyping' is becoming more common in clinical practice as it offers the hope of personalized targeted therapy. We wanted to evaluate the results and the clinical utility of available nextgeneration sequencing panels in WD/DD liposarcoma. Patients who had their tumor sequenced by either FoundationOne (n = 13) or the institutional T200/T200.1 panels (n = 7) were included in this study. Significant copy number alterations were identified, but mutations were infrequent. Out of the 27 mutations detected in 7 samples, 8 (CTNNB1, MECOM, ZNF536, EGFR, EML4, CSMD3, PBRM1, PPP1R3A) were identified as deleterious (on Condel, PolyPhen and SIFT) and a truncating mutation was found in NF2. Of these, EGFR and NF2 are potential driver mutations and have not been reported previously in liposarcoma. MDM2 and CDK4 amplification was universally present in all the tested samples and multiple other recurrent genes with high amplification or high deletion were detected. Many of these targets are potentially actionable. Eight patients went on to receive an MDM2 inhibitor with a median time to progression of 23 months (95% CI: 10-83 months).
KW - MDM2 inhibitors
KW - Targeted therapy
KW - Well-differentiated and dedifferentiated liposarcoma sequencing
UR - http://www.scopus.com/inward/record.url?scp=85045331226&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045331226&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.24924
DO - 10.18632/oncotarget.24924
M3 - Article
C2 - 29731991
AN - SCOPUS:85045331226
SN - 1949-2553
VL - 9
SP - 19891
EP - 19899
JO - Oncotarget
JF - Oncotarget
IS - 28
ER -