Next-generation Sequencing Identified a Novel WDPCP-ALK Fusion Sensitive to Crizotinib in Lung Adenocarcinoma

He, Zhen; Wu, Xuan; Ma, Shijing; Zhang, Cuicui; Zhang, Zhe; Wang, Shuai; Yu, Shanshan; Wang, Qiming

doi:10.1016/j.cllc.2019.06.001

Cited by 9 publications

(3 citation statements)

References 9 publications

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“…In NSCLC, targeting of non-EML4 ALK fusions that retained the tyrosine kinase domain, including WDPCP-ALK, NCOA1-ALK, and CUX1-ALK, with crizotinib has resulted in partial response (27)(28)(29). The success of the ALK inhibitor crizotinib in improving clinical outcomes in patients with ALK-rearranged advanced NSCLC prompted us to administer crizotinib at the standard dose approved for treatment in advanced NSCLC to our patient with GBC harboring AMBRA1-ALK rearrangement.…”

Section: Discussionmentioning

confidence: 99%

Novel AMBRA1-ALK fusion identified by next-generation sequencing in advanced gallbladder cancer responds to crizotinib: a case report

et al. 2020

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Gallbladder cancer (GBC) is the most aggressive malignancy of the biliary tract with poor prognosis. Several targetable genetic alterations have been identified in GBC; however, responses to targeted therapy are disappointing. We report a case of a 58-year-old Chinese woman with GBC who was detected with a novel ALK genomic rearrangement and received crizotinib after progression from first-line chemotherapy. The patient was diagnosed with stage IV adenocarcinoma of the neck of the gallbladder and received oxaliplatin combined with capecitabine as first-line therapy. After four cycles of this chemotherapy regimen, the patient started to show obstructive jaundice, and progressive disease was evaluated. Biliary drainage surgery was performed to alleviate the symptoms of obstructive jaundice. Upon referral to our department, her archived tissue samples were submitted for next-generation sequencing (Burning Rock Biotech) and immunohistochemistry, which identified the presence of a novel AMBRA1-ALK rearrangement and ALK overexpression, respectively. Oral crizotinib was administered achieving partial response within two cycles of treatment, which lasted for 7 months. AMBRA1-ALK has not been previously reported in any solid tumors and its sensitivity to crizotinib is not well characterized. Moreover, ALK alterations have been rarely reported for GBC. This case suggests that a subset of GBC might be driven by aberrant ALK signaling, which could potentially be explored as a biomarker of therapeutic response to ALK inhibitors in GBC. Moreover, our case report contributes an incremental step in understanding the genetic heterogeneity in GBC and provides clinical evidence of the utility of next-generation sequencing in exploring actionable mutations to expand treatment choices in rare solid tumors including GBC.

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Section: Discussionmentioning

confidence: 99%

Novel AMBRA1-ALK fusion identified by next-generation sequencing in advanced gallbladder cancer responds to crizotinib: a case report

et al. 2020

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“…Furthermore, both ROS1 and RET fusions are quite similar to ALK rearrangement cases 61 . Lately, a novel Trp‐ASP planar cell polarity (WD‐PCP)‐ALK gene fusion in lung adenocarcinoma is also sensitive to the ALK inhibitor 62 . For the clinical diagnosis of NSCLC, multiplexed NGS and gene fusion diagnostics are feasible and indispensable, which can indicate a significant proportion of patients who may be eligible for the emerging molecular therapies.…”

Section: The Application Of Ngs Platform In Tumor Therapymentioning

confidence: 99%

The importance of precision medicine in modern molecular oncology

Wang

Zheng

2021

Clinical Genetics

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With the rapid development of modern medical technology, information data modeling has been gradually applied to clinical diagnosis and treatment. Precision medicine is an important approach that focuses on individual patients in terms of their own characteristics, genomic information, proteomics and even social environments. Genome‐wide high‐throughput technologies, including DNA‐seq, RNA‐seq, exosome‐seq…, contribute enormous amounts of molecular data to aid in diagnosis and analysis. Here, we review the developmental history of different next‐generation sequencing platforms, introduce their applications in different tumor diagnosis and therapy, and further discuss the remaining challenges in precision medicine.

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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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Next-generation Sequencing Identified a Novel WDPCP-ALK Fusion Sensitive to Crizotinib in Lung Adenocarcinoma

Abstract: Figure 4 WDPCP-ALK Fusion and C1156Y-ALK Were Identified by Next-generation Sequencing Abbreviations: ALK ¼ anaplastic lymphoma kinase; WDPCP ¼ WD planar cell polarity effector gene.

Cited by 9 publications

References 9 publications

Novel AMBRA1-ALK fusion identified by next-generation sequencing in advanced gallbladder cancer responds to crizotinib: a case report

Novel AMBRA1-ALK fusion identified by next-generation sequencing in advanced gallbladder cancer responds to crizotinib: a case report

The importance of precision medicine in modern molecular oncology

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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