Response to <scp>ALK‐TKIs</scp> in a lung adenocarcinoma patient harboring dual <scp><i>DCTN1‐ALK</i></scp> and <scp><i>ALK‐CLIP4</i></scp> rearrangements

Gao, Fangfang; Wu, Huijuan; Lu, Junfeng; Xu, Yaping; Zhao, Yanqiu

doi:10.1111/1759-7714.14345

Cited by 4 publications

(5 citation statements)

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“…This fusion has been seen to be recurrent in CAF in small studies. 13 The FN1::EGF fusion has only been observed in CAF and not in other types of neoplasms and small studies indicate it is the main driver mutation in CAF. 21 However, further functional studies need to be conducted to determine the mechanism of cancer onset in CAF tumors 21 and therefore it cannot yet be classified as a tier I fusion (see Figure 3 ).…”

Section: Discussionmentioning

confidence: 99%

“… 6 Conversely, there remains continued debate about which fusion genes are of clinical value and are considered actionable, particularly when more than 1 fusion is discovered in a single tumor sample. 7 , 8 Several studies have demonstrated multiple fusions in single tumor samples, predominantly in hematopoietic 9 - 11 and epithelial 12 - 15 malignancies. While similar findings have been reported in soft tissue samples, 16 the incidence of multiple fusions in single PSTBT samples has not been well documented.…”

Section: Introductionmentioning

confidence: 99%

“… 16 However, some tumors have multiple fusions with therapeutic relevance. 11 - 13 Thus, the classification of fusions according to potential clinical significance is of paramount importance. There is a well-known scheme for classifying and reporting sequence variants in cancer, including SNVs, CNVs, and structural variants, based on criteria published by the American Society of Clinical Oncology and College of American Pathologists.…”

Section: Introductionmentioning

confidence: 99%

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The Incidence of Multiple Fusions in a Series of Pediatric Soft Tissue and Bone Tumors

MacKeracher,

Arnoldo,

Siddaway

et al. 2023

Pediatr Dev Pathol

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Background: Next generation sequencing (NGS) has increased the detection of fusion genes in cancer. NGS has found multiple fusions in single tumor samples; however, the incidence of this in pediatric soft tissue and bone tumors (PSTBTs) is not well documented. The aim of this study is to catalogue the incidence of multiple fusions in a series of PSTBTs, and apply a modified gene fusion classification system to determine clinical relevance. Methodology: RNA from 78 bone and soft tissue tumors and 7 external quality assessment samples were sequenced and analyzed using recently-described Metafusion (MF) software and classified using a modification of previously-published schema for fusion classification into 3 tiers: 1, strong clinical significance; 2, potential clinical significance; and 3, unknown clinical significance. Results: One-hundred forty-five fusions were detected in 85 samples. Fifty-five samples (65%) had a single fusion and 30 (35%) had more than 1 fusion. No samples contained more than 1 tier 1 fusion. There were 40 tier 1 (28%), 36 tier 2 (24%), and 69 (48%) tier 3 fusions. Conclusions: A significant percentage of PSTBTs harbor more than 1 fusion, and by applying a modified fusion classification scheme, the potential clinical relevance of such fusions can be determined.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Incidence of Multiple Fusions in a Series of Pediatric Soft Tissue and Bone Tumors

MacKeracher,

Arnoldo,

Siddaway

et al. 2023

Pediatr Dev Pathol

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“…Five patients developed ALK fusion, including a rare fusion type DCTN1/ALK (D24: A20). Gao Fangfang, et al (19) have reported that one case of DCTN1/ALK achieved partial response after receiving cabozantinib therapy. ERBB2, RET, ROS1, PIK3CA, BRAF, and NRAS were detected in older LUAD patients.…”

Section: Discussionmentioning

confidence: 99%

Relationship between driver gene mutations and clinical pathological characteristics in older lung adenocarcinoma

Liu,

Jiang,

Sun

et al. 2023

Front. Oncol.

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ObjectivesLung adenocarcinoma (LUAD) is the most common newly diagnosed malignant tumor in older people. As older patients age, organ function decreases, leading to increased adverse reactions to treatment. The epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase tyrosine (ALK) tyrosine kinase inhibitors (TKIs) therapy are more effective and well-tolerated than chemotherapy, while the rate of genetic testing and subsequent targeted treatment among older patients remains relatively low, the clinical benefit limitation for those patients. This study aims to investigate the mutation characteristics of LUAD diver gene and its relationship with clinicopathological features in older LUAD.Materials and methodsA total of 275 patients were diagnosed as LUAD and were over sixty years old. We utilized next-generation sequencing technology to detect and analyze gene mutations in postoperative tissue specimens, including EGFR, KRAS, ALK, ROS1, RET, MET, BRAF, HER2, PIK3CA and NRAS.ResultsA total of 90.18% (248/275) of older LUAD patients experienced genetic mutations. The EGFR (192, 69.82%) had the highest mutation rate among ten genes, followed by KRAS (21, 7.64%), MET (21, 7.64%), ERBB2 (15, 5.45%), RET (9, 3.27%), ALK (8, 2.91%), ROS1 (8, 2.91%), PIK3CA (6, 2.18%), BRAF (5, 1.82%) and NRAS (1, 0.36%). We also found thirty patients (15.63%) with EGFR mutations also having other gene mutations. The L858R mutation and exon19 deletion were the predominant EGFR mutations, accounting for 84.90% of EGFR-mutated patients. In addition, fifty-one kinds of EGFR mutations were detected, distributed in the protein tyrosine kinase catalytic domain (43, 84.31%), cysteine enriched domain (4, 7.84%), receptor binding domain (3, 5.88%), and EGFR transmembrane domain (1,1.96%). Ten cases of gene fusion mutation were detected. Two rare partner genes, PKHD1 (P60:R34) and STK39 (R33:S11), were detected by ROS1 gene fusion. RET gene fusion revealed a rare companion gene KCND2 (R11:K2). The EGFR mutations were more prevalent in female, non-smoking patients (p < 0.05), and the KRAS mutations were more common in male and smoking patients (p < 0.01). In addition, the BRAF mutations were more likely to occur in the right lung (p < 0.05).ConclusionOlder LUAD populations exhibit diverse genetic mutations, which may also exist simultaneously. Simultaneous detection of multiple genes by NGS can accelerate and enhance targeted treatment benefits for older LUAD patients, ultimately improving their quality of life.

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“…Concurrent presence of 2 or more ALK-fusion forms is rare. [2,3] Echinoderm microtubule-associated protein 4 (EML4) is the most frequently fusion partner of ALK fusion. [4] Additionally, brain metastasis occurs in approximately 23% to 31% of patients with ALK-fusion NSCLC and is associated with a poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Lung adenocarcinoma with brain metastasis detected dual fusion of LOC399815-ALK and ALK-EML4 in combined treatment of Alectinib and CyberKnife: A case report

Li,

Lu,

Yao

et al. 2024

Medicine

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Introduction: The anaplastic lymphoma kinase (ALK) gene fusion occurs in approximately 3% to 7% of nonsmall cell lung cancer (NSCLC), in which occurs approximately 23% to 31% of brain metastasis patients in poor prognosis. ALK tyrosine kinase inhibitors have shown efficacy in treating ALK-positive (ALK+) NSCLC. More than 90 distinct subtypes of ALK fusions have been identified through sequencing technique and would lead to significant differences in clinical efficacy, it is necessary to guide clinical treatment effectively by gene detection. Patient concerns: A 56-year-old nonsmoking female admitted to hospital due to cough, expectoration, and chest pain. Chest computed tomography revealed a space-occupying lesion in the upper left lobe (5.0 cm × 2.4 cm × 2.9 cm), multiple enlarged lymph nodes in mediastinum 3A and 5 (largest size 1.5 cm × 1.4 cm), and evidence of thoracic vertebral metastasis, brain magnetic resonance imaging also showed brain metastasis. Diagnoses: Lung adenocarcinoma with brain metastasis. Interventions: The patient initially received conventional first-line chemotherapy, which led to a deteriorated condition. Blood-base liquid biopsy by next-generation sequencing resulted in double ALK fusions, in which with a neo-partner of lncRNA (LOC399815-ALK). Following subsequent treatment with Alectinib and stereotactic radiotherapy (CyberKnife) was subsequently employed to manage the brain metastatic lesions, resulting in a substantial decreased in both the number and size of tumor lesions. Outcomes: The patient’s response to therapy efficacy resulted in a substantial decreased in both the number and size of tumor lesions that assessed comprehensively evaluated through computed tomography imaging and ctDNA sequencing. Patient’s condition has been under control for over 29 months. Conclusion: Liquid biopsy may reveal the rare fusion forms of ALK, precisely guiding personalized treatment, and providing a reference method for longitudinal monitoring and efficacy evaluation of ALK-tyrosine kinase inhibitors in NSCLC patients.

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Response to ALK‐TKIs in a lung adenocarcinoma patient harboring dual DCTN1‐ALK and ALK‐CLIP4 rearrangements

Cited by 4 publications

References 7 publications

The Incidence of Multiple Fusions in a Series of Pediatric Soft Tissue and Bone Tumors

The Incidence of Multiple Fusions in a Series of Pediatric Soft Tissue and Bone Tumors

Relationship between driver gene mutations and clinical pathological characteristics in older lung adenocarcinoma

Lung adenocarcinoma with brain metastasis detected dual fusion of LOC399815-ALK and ALK-EML4 in combined treatment of Alectinib and CyberKnife: A case report

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