Chromoplectic TPM3-ALK rearrangement in a patient with inflammatory myofibroblastic tumor who responded to ceritinib after progression on crizotinib.
Chromoplectic TPM3-ALK rearrangement in a patient with inflammatory myofibroblastic tumor who responded to ceritinib after progression on crizotinib.
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DOI：
10.1093/annonc/mdw405
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Jen J
中科院分区：
文献类型：
--
作者：
Mansfield AS;Murphy SJ;Harris FR;Robinson SI;Marks RS;Johnson SH;Smadbeck JB;Halling GC;Yi ES;Wigle D;Vasmatzis G;Jen J
在克唑替尼失败后，色瑞替尼对转移性炎性肌纤维母细胞瘤 (IMT) 产生了显着、持久的反应。在残留的 IMT 中发现了涉及许多已知癌基因的色素 TPM3-ALK 重排。色瑞替尼可能对克唑替尼失败后出现 IMT 的患者有用，并且染色体可能在 IMT 的肿瘤发生或治疗耐药中发挥作用。炎性肌纤维母细胞瘤（IMT）是罕见的肉瘤，可发生于任何年龄。手术切除是局部病变患者的主要治疗方法；然而，这些肿瘤经常复发。不太常见的是，IMT 患者出现或出现转移性疾病。这些患者没有标准的护理，传统的细胞毒疗法基本上无效。大多数 IMT 与致癌 ALK、ROS1 或 PDGFRβ 融合相关，可能受益于靶向治疗。我们试图了解一名患者的基因组异常情况，该患者在接受克唑替尼治疗病情进展后接受转移性 IMT 治疗，并对更有效的 ALK 抑制剂色瑞替尼产生显着且持久的部分反应。根据多学科肿瘤肉瘤肿瘤委员会的建议切除残留的 IMT，并通过全基因组配对测序进行分析。对切除的残余肿瘤的分析发现了染色质 TPM3-ALK 重排，该重排涉及许多其他已知的癌基因，并通过 rtPCR 得到了证实。在我们对治疗耐药的残余 IMT 的分析中，我们发现了与染色体复合体一致的复杂的基因重排模式。尽管很难确定这些色素重排是否发生在治疗之前，但它们的存在表明色素丛在 IMT 的肿瘤发生中发挥作用。此外，该患者的显着反应表明，对于患有转移性或不可切除的 IMT 和 ALK 突变的患者，在使用克唑替尼治疗病情进展后，应考虑将色瑞替尼作为一种选择。
Ceritinib resulted in a significant, durable response of a metastatic inflammatory myofibroblastic tumor (IMT) after failure of crizotinib. A chromoplectic TPM3–ALK rearrangement involving many known oncogenes was found in the residual IMT. Ceritinib may be useful for patients with IMT after failure of crizotinib, and chromoplexy may have a role in the oncogenesis or treatment resistance of IMTs. Inflammatory myofibroblastic tumors (IMTs) are rare sarcomas that can occur at any age. Surgical resection is the primary treatment for patients with localized disease; however, these tumors frequently recur. Less commonly, patients with IMTs develop or present with metastatic disease. There is no standard of care for these patients and traditional cytotoxic therapy is largely ineffective. Most IMTs are associated with oncogenic ALK, ROS1 or PDGFRβ fusions and may benefit from targeted therapy. We sought to understand the genomic abnormalities of a patient who presented for management of metastatic IMT after progression of disease on crizotinib and a significant and durable partial response to the more potent ALK inhibitor ceritinib. The residual IMT was resected based on the recommendations of a multidisciplinary tumor sarcoma tumor board and analyzed by whole-genome mate pair sequencing. Analysis of the residual, resected tumor identified a chromoplectic TPM3–ALK rearrangement that involved many other known oncogenes and was confirmed by rtPCR. In our analysis of the treatment-resistant, residual IMT, we identified a complex pattern of genetic rearrangements consistent with chromoplexy. Although it is difficult to know for certain if these chromoplectic rearrangements preceded treatment, their presence suggests that chromoplexy has a role in the oncogenesis of IMTs. Furthermore, this patient's remarkable response suggests that ceritinib should be considered as an option after progression on crizotinib for patients with metastatic or unresectable IMT and ALK mutations.
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DOI：
10.1093/dnares/dss021
发表时间：
2012-10
期刊：
DNA research : an international journal for rapid publication of reports on genes and genomes
影响因子：
--
作者：
Murphy SJ;Cheville JC;Zarei S;Johnson SH;Sikkink RA;Kosari F;Feldman AL;Eckloff BW;Karnes RJ;Vasmatzis G
通讯作者：
Vasmatzis G
影响因子：
28.2
作者：
Friboulet L;Li N;Katayama R;Lee CC;Gainor JF;Crystal AS;Michellys PY;Awad MM;Yanagitani N;Kim S;Pferdekamper AC;Li J;Kasibhatla S;Sun F;Sun X;Hua S;McNamara P;Mahmood S;Lockerman EL;Fujita N;Nishio M;Harris JL;Shaw AT;Engelman JA
通讯作者：
Engelman JA
DOI：
10.1056/nejmoa1007056
发表时间：
2010-10-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Butrynski JE;D'Adamo DR;Hornick JL;Dal Cin P;Antonescu CR;Jhanwar SC;Ladanyi M;Capelletti M;Rodig SJ;Ramaiya N;Kwak EL;Clark JW;Wilner KD;Christensen JG;Jänne PA;Maki RG;Demetri GD;Shapiro GI
通讯作者：
Shapiro GI
影响因子：
28.2
作者：
Lovly CM;Gupta A;Lipson D;Otto G;Brennan T;Chung CT;Borinstein SC;Ross JS;Stephens PJ;Miller VA;Coffin CM
通讯作者：
Coffin CM
影响因子：
6
作者：
Lawrence, B;Perez-Atayde, A;Fletcher, JA
通讯作者：
Fletcher, JA