A new<i>KIF5B</i>–<i>ERBB4</i>gene fusion in a lung adenocarcinoma patient

Guenzi, Edouard; Pluvy, Johan; Guyard, Alice; Nguenang, Marina; Rebah, Khedidja; Benrahmoune, Zoubida; Lamoril, J.; Cazes, Aurélie; Gounant, V.; Brosseau, Solenn; Boileau, Cathérine; Zalcman, Gérard; Théou–Anton, Nathalie

doi:10.1183/23120541.00582-2020

Cited by 7 publications

(6 citation statements)

References 10 publications

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“…While CIQTNF1-ERBB4 translocations have not previously been reported, fusions involving ERBB4 have been infrequently described in lung adenocarcinoma (with EZR/KIF5B), T-cell lymphoma (with IKZF2), and oropharyngeal squamous cell carcinoma (with B4GALT5) (19). ERBB4 is part of the ErbB/ ATPase domain is retained Breakpoint starts here in ERBB4 (codon 28 onwards are retained) HER family of protein tyrosine kinases.…”

Section: Discussionmentioning

confidence: 99%

Description of a Novel ERBB4-rearranged Uterine Sarcoma

Lim

Mansor

Kathirvel

et al. 2021

International Journal of Gynecological Pathology

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High-grade endometrial stromal sarcoma (HGESS) is an uncommon tumor accounting for <1% of all uterine malignancies. Currently this designation is largely reserved for neoplasms harboring YWHAE-NUTM2A/B and ZC3H7B-BCOR translocations. Here, we report a novel CIQTNF1-ERBB4 translocation in a uterine neoplasm arising in a 49-yr-old woman with morphology suggestive of HGESS. Histologic examination of the 5 cm polypoid uterine corpus mass showed a neoplasm composed of a monotonous population of cells with moderately atypical ovoid to spindle shaped nuclei with easily identifiable mitotic activity and prominent vasculature with focal intravascular extension. Immunohistochemistry showed variable positivity with desmin, estrogen receptor, progesterone receptor, AE1/3 and cyclin D1, and molecular testing showed a translocation between CIQTNF1 on chromosome 17 and ERBB4 on chromosome 2. This represents the first report of this translocation in a uterine neoplasm and adds to the growing list of translocations identified in uterine sarcomas. Although the morphology is suggestive of HGESS, this neoplasm is currently best termed an ERBB4-rearranged uterine sarcoma until additional cases are reported to more fully characterize these neoplasms.

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Section: Discussionmentioning

confidence: 99%

Description of a Novel ERBB4-rearranged Uterine Sarcoma

Lim

Mansor

Kathirvel

et al. 2021

International Journal of Gynecological Pathology

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“…This finding is in contrast to lung cancer-associated EGFR mutations, most of which typically target few sites in the kinase domain ( Figure 2 ). Additionally, rare ERBB4 fusions with different fusion partners have been described in NSCLC 174 , 175 . All these fusion proteins retain the full ERBB4 kinase domain and lead to dimerization of 2 HER4-containing fusion proteins and subsequent aberrant activation of the HER4 kinase domain 174 .…”

Section: The Her4 (Erbb4) Receptormentioning

confidence: 99%

Targeting the EGF receptor family in non-small cell lung cancer—increased complexity and future perspectives

et al. 2022

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Lung cancer remains the leading cause of cancer-associated mortality worldwide, but with the emergence of oncogene targeted therapies, treatment options have tremendously improved. Owing to their biological relevance, members of the ERBB receptor family, including the EGF receptor (EGFR), HER2, HER3 and HER4, are among the best studied oncogenic drivers. Activating EGFR mutations are frequently observed in non-small cell lung cancer (NSCLC), and small molecule tyrosine kinase inhibitors (TKIs) are the established first line treatment option for patients whose tumors bear “typical/classical” EGFR mutations (exon 19 deletions, L858R point mutations). Additionally, new TKIs are rapidly evolving with better efficacy to overcome primary and secondary treatment resistance (e.g., that due to T790M or C797S resistance mutations). Some atypical EGFR mutations, such as the most frequent exon 20 insertions, exhibit relative resistance to earlier generation TKIs through steric hindrance. In this subgroup, newer TKIs, such as mobocertinib and the bi-specific antibody amivantamab have recently been approved, whereas less frequent atypical EGFR mutations remain understudied. In contrast to EGFR, HER2 has long remained a challenging target, but better structural understanding has led to the development of newer generations of TKIs. The recent FDA approval of the antibody-drug conjugate trastuzumab-deruxtecan for pretreated patients with HER2 mutant NSCLC has been an important therapeutic breakthrough. HER3 and HER4 also exert oncogenic potential, and targeted treatment approaches are being developed, particularly for HER3. Overall, strategies to inhibit the oncogenic function of ERBB receptors in NSCLC are currently evolving at an unprecedented pace; therefore, this review summarizes current treatment standards and discusses the outlook for future developments.

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“…These findings suggest that targeting KIF5B-RET may be considered as a potential approach for the clinical treatment of patients with lung adenocarcinoma (LUAD). [104][105][106][107] Li's article suggests that Biochanin A, a naturally occurring isoflavone, has been demonstrated to exhibit anticancer effects in various tumors, including lung adenocarcinoma. Biochanin A could specifically inhibit the expression of ZEB1, which is associated with both chemoresistance and metastasis.…”

Section: Introductionmentioning

confidence: 99%

“…These findings suggest that targeting KIF5B-RET may be considered as a potential approach for the clinical treatment of patients with lung adenocarcinoma (LUAD). 104–107…”

Section: Introductionmentioning

confidence: 99%

A graphSAGE discovers synergistic combinations of Gefitinib, paclitaxel, and Icotinib for Lung adenocarcinoma management by targeting human genes and proteins: the RAIN protocol

Sadeghi,

Kiaei,

Boush

et al. 2024

Preprint

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Background: Adenocarcinoma of the lung is the most common type of lung cancer, and it is characterized by distinct cellular and molecular features. It occurs when abnormal lung cells multiply out of control and form a tumor in the outer region of the lungs. Adenocarcinoma of the lung is a serious and life-threatening condition that requires effective and timely management to improve the survival and quality of life of the patients. One of the challenges in this cancer treatment is finding the optimal combination of drugs that can target the genes or proteins that are involved in the disease process. Method: In this article, we propose a novel method to recommend combinations of trending drugs to target its associated proteins/genes, using a Graph Neural Network (GNN) under the RAIN protocol. The RAIN protocol is a three-step framework that consists of: 1) Applying graph neural networks to recommend drug combinations by passing messages between trending drugs for managing disease and genes that act as potential targets for disease; 2) Retrieving relevant articles with clinical trials that include those proposed drugs in previous step using Natural Language Processing (NLP); 3) Analyzing the network meta-analysis to measure the comparative efficacy of the drug combinations. Result: We applied our method to a dataset of nodes and edges that represent the network, where each node is a drug or a gene, and each edge is a p-value between them. We found that the graph neural network recommends combining Gefitinib, Paclitaxel, and Icotinib as the most effective drug combination to target this cancer associated proteins/genes. We reviewed the clinical trials and expert opinions on these medications and found that they support our claim. The network meta-analysis also confirmed the effectiveness of these drugs on associated genes. Conclusion: Our method is a novel and promising approach to recommend trending drugs combination to target cancer associated proteins/genes, using graph neural networks under the RAIN protocol. It can help clinicians and researchers to find the best treatment options for patients, and also provide insights into the underlying mechanisms of the disease.

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A newKIF5B–ERBB4gene fusion in a lung adenocarcinoma patient

Cited by 7 publications

References 10 publications

Description of a Novel ERBB4-rearranged Uterine Sarcoma

Description of a Novel ERBB4-rearranged Uterine Sarcoma

Targeting the EGF receptor family in non-small cell lung cancer—increased complexity and future perspectives

A graphSAGE discovers synergistic combinations of Gefitinib, paclitaxel, and Icotinib for Lung adenocarcinoma management by targeting human genes and proteins: the RAIN protocol

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