In:
Oncology, S. Karger AG, Vol. 90, No. 6 ( 2016), p. 339-346
Abstract:
〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 The aim of this study was to determine the genomic alterations of cancer-related genes in advanced medullary thyroid carcinoma during the course of clinical care. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Hybrid-capture-based comprehensive genomic profiling was performed on 34 consecutive medullary thyroid carcinoma cases to identify all four classes of genomic alterations, and outcome for an index patient was collected. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 〈 i 〉 RET 〈 /i 〉 was mutated in 88% (30/34) of cases, with 〈 i 〉 RET 〈 /i 〉 M918T being responsible for 70% (21/30) of the 〈 i 〉 RET 〈 /i 〉 alterations. The other 〈 i 〉 RET 〈 /i 〉 alterations were 〈 i 〉 RET 〈 /i 〉 E632_L633del, C634R, C620R, C618G/R/S, V804M, and 〈 i 〉 RET 〈 /i 〉 amplification. Two of the four 〈 i 〉 RET 〈 /i 〉 wild-type patients harbored mutations in 〈 i 〉 KRAS 〈 /i 〉 or 〈 i 〉 HRAS 〈 /i 〉 (1/34 each). The next most frequent genomic alterations were amplifications of 〈 i 〉 CCND1 〈 /i 〉 , 〈 i 〉 FGF3 〈 /i 〉 , and 〈 i 〉 FGF19 〈 /i 〉 and alterations in 〈 i 〉 CDKN2A 〈 /i 〉 (3/34 each). One case with a 〈 i 〉 RET 〈 /i 〉 M918T mutation developed acquired resistance to progressively dose-escalated vandetanib. When the mTOR inhibitor everolimus was added to continued vandetanib treatment, the patient achieved a second 25% reduction of tumor volume (RECIST 1.1) for 8 months. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Comprehensive genomic profiling identified the full breadth of 〈 i 〉 RET 〈 /i 〉 alterations in metastatic medullary thyroid carcinoma and possible cooperating oncogenic driver alterations. This approach may refine the use of targeted therapy for these patients.
Type of Medium:
Online Resource
ISSN:
0030-2414
,
1423-0232
Language:
English
Publisher:
S. Karger AG
Publication Date:
2016
detail.hit.zdb_id:
1483096-6
detail.hit.zdb_id:
250101-6
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