PLEKHM2-ALK: A novel fusion in small-cell lung cancer and durable response to ALK inhibitors

Li, Tao; Zhang, Fan; Wu, Zhaozhen; Cui, Longgang; Zhao, Xiaochen; Wang, Jinliang; Hu, Yi

doi:10.1016/j.lungcan.2019.11.002

Cited by 15 publications

(7 citation statements)

References 6 publications

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“…The PLEKHH2::ALK fusion has only been extremely rarely reported to date, with a majority of reports in lung adenocarcinoma and only a single abstract reporting this finding in an IMT. [8][9][10] In lung adenocarcinoma, patients with this rare fusion have been identified as having a durable response to ALK inhibitors. 9,10 Sarcomas with 5′ ALK loss, such as in the gene rearrangement identified here and in the single previously reported IMT with PLEKHH2::ALK fusion, have also been associated with an improved response to ALK inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] In lung adenocarcinoma, patients with this rare fusion have been identified as having a durable response to ALK inhibitors. 9,10 Sarcomas with 5′ ALK loss, such as in the gene rearrangement identified here and in the single previously reported IMT with PLEKHH2::ALK fusion, have also been associated with an improved response to ALK inhibitors. 8,11 Importantly, this susceptibility to ALK inhibition held true in the presented case, substantiating this finding in a second mesenchymal neoplasm with PLEKHH2:: ALK fusion.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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S100 and CD34 Expressing Mesenchymal Neoplasm With Rare PLEKHH2::ALK Fusion and Response to ALK Inhibition

Coppock¹,

Schneider

Surrey

et al. 2022

American Journal of Surgical Pathology

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The PLEKHH2::ALK fusion is a rarely reported gene fusion identified predominantly in lung adenocarcinomas. Tumors with this fusion have been reported to be of durable response to ALK inhibitors. We herein present the case of a 21-year-old woman with a histomorphologically heterogenous mesenchymal neoplasm of the pelvis, expressing both s100 and CD34, with subsequently identified PLEKHH2::ALK fusion. To our knowledge, only a single mesenchymal neoplasm with this gene fusion has been previously reported. We propose that this tumor represents one with a novel ALK fusion in the emerging family of s100 and CD34 expressing mesenchymal neoplasms with oncogenic kinase alterations akin to NTRK-rearranged mesenchymal neoplasms, rather than inflammatory myofibroblastic tumor. Importantly, this tumor demonstrated a significant response to the ALK inhibitor brigatinib.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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S100 and CD34 Expressing Mesenchymal Neoplasm With Rare PLEKHH2::ALK Fusion and Response to ALK Inhibition

Coppock¹,

Schneider

Surrey

et al. 2022

American Journal of Surgical Pathology

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“…36,37 Therefore, when patients are pathologically diagnosed as locally advanced or metastatic NSCLC, or adenosquamous carcinoma containing adenocarcinoma components or even combined small-cell lung cancer (C-SCLC) 38 ; patients develop drug resistance after EGFR-TKI and ALK-TKI treatments; and patients with invasive adenocarcinoma are pathologically confirmed after surgery, RET rearrangement detection is recommended if possible. 26,39…”

Section: Population Undergoing Ret Rearrangement Detectionmentioning

confidence: 99%

Advances in the Diagnosis and Treatment of a Driving Target: RET Rearrangements in non-Small-Cell Lung Cancer (NSCLC) Especially in China

Yang

Liu

et al. 2023

Technol Cancer Res Treat

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In the era of precision medicine, with the deepening of the research on malignant tumor driving genes, clinical oncology has fully entered the era of targeted therapy. For non-small-cell lung cancer (NSCLC), the development of targeted drugs targeting driver genes, such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has successfully opened up a new model of targeted therapy. At present, proto-oncogene rearranged during transfection (RET) fusion gene is an important novel oncogenic driving target, and specific receptor tyrosine kinase inhibitors (TKIs) targeting RET fusion have been approved. This article will review the latest research about the molecular characteristics, pathogenesis, detection, and clinical treatment strategies of RET rearrangements especially in China.

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“…ALK rearrangement is usually taken into consideration when deciding on the administration of ALK-TKIs for the management of NSCLC. With the popularity of next-generation sequencing (NGS) technology, besides EML4-ALK, other rearrangement types sensitive to ALK-TKIs, including SPECC1L-ALK, PLEKHM2-ALK, and WDPCP-ALK, have been detected (3)(4)(5); however, the case with ALK double rearrangement is rare (6). Also, considering the disparate clinical outcome of different ALK variants, it is imperative to test the response of both double and new types of rearrangement to ALK-TKIs.…”

Section: Introductionmentioning

confidence: 99%

Coexistence of a novel CCNY-ALK and ATIC-ALK double-fusion in one patient with ALK-positive NSCLC and response to crizotinib: a case report

Wu¹,

Zhou²,

He³

et al. 2020

Transl Lung Cancer Res

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Anaplastic lymphoma kinase (ALK) rearrangement, one of the common oncogene rearrangements in the mutational history of lung adenocarcinoma, occurs in approximately 5% of non-small cell lung cancer (NSCLC) patients who could be effectively treated with ALK tyrosine kinase inhibitors (TKIs). The earlier phase III PROFILE 1014 study has shown that crizotinib, a first-generation ALK-TKI, significantly improved progression-free survival (PFS) compared with platinum-based chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. Thus, clinicians must screen potential candidates for this driver alteration to guide ALK inhibitor therapy with a molecular testing platform capable of capturing all ALK fusions. Echinoderm microtubule-associated proteins, including the EML4 gene, are the most common ALK rearrangement partner. With the widespread use of the next-generation sequencing (NGS) techniques, which could approach enable the simultaneous screening of multiple genetic alterations, increasingly ALK rearrangement partners have been documented. However, the concurrent two ALK rearrangements within the same patient have rarely previously been reported. Here, we describe a novel CCNY-ALK (C1:A20) and ATIC-ALK (A7:A20), coexisting in the same case with poorly differentiated NSCLC and providing evidence of its sensitivity to ALK inhibitors. The newly identified rearrangement partners can be added to the list of ALK rearrangements that occurred in ALK-positive NSCLC, as it could lead to prolonged disease control. Also, while different ALK rearrangement variants might bring differing clinical outcomes, we discuss the impact of the co-mutations of these two ALK rearrangements on the sensitivity to ALK inhibitors. However, the impact of co-mutations on the pathogenesis of NSCLC should be further studied to supply more theoretical insight that co-mutations present for personalized anti-cancer therapy.

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PLEKHM2-ALK: A novel fusion in small-cell lung cancer and durable response to ALK inhibitors

Cited by 15 publications

References 6 publications

S100 and CD34 Expressing Mesenchymal Neoplasm With Rare PLEKHH2::ALK Fusion and Response to ALK Inhibition

S100 and CD34 Expressing Mesenchymal Neoplasm With Rare PLEKHH2::ALK Fusion and Response to ALK Inhibition

Advances in the Diagnosis and Treatment of a Driving Target: RET Rearrangements in non-Small-Cell Lung Cancer (NSCLC) Especially in China

Coexistence of a novel CCNY-ALK and ATIC-ALK double-fusion in one patient with ALK-positive NSCLC and response to crizotinib: a case report

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