Case Report: RAB10-ALK: A Novel ALK Fusion in a Patient With Gastric Cancer

Zhou, Wen; Xiong, Dun; Zhang, Shurong; Liu, Jiankun; Li, Bitao; Li, Raomei; Zhang, Hushan

doi:10.3389/fonc.2021.645370

Cited by 7 publications

(4 citation statements)

References 9 publications

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“…Nonetheless, both studies demonstrated the rarity of ALK positivity in gastric cancer. Recently, a novel RAB10-ALK fusion was reported in a Chinese patient with gastric cancer, 12 and this is the second and third case report of ALK fusion in gastric cancer.…”

Section: Discussionmentioning

confidence: 79%

Two Gastric Cancers With Uncommon ALK Fusion Diagnosed With Comprehensive Panel Sequencing and Confirmed With Companion Diagnostic Assay

Kim¹,

Ahn²,

Kang

et al. 2022

AJSP: Reviews and Reports

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ALK gene rearrangement is clinically significant due to the ALK tyrosine kinase inhibitor, important in several types of ALKrearranged malignancies, most prominently in non-small cell lung cancers. ALK fusion in the gastrointestinal tract is rare. Herein, we report 2 cases of gastric cancer, in which ALK is fused with two uncommon partners, SLMAP and STRN. Two cases of ALK fusion were identified by comprehensive panel sequencing of 231 clinical gastric cancer samples. The results were confirmed using the Ventana ALK (D5F3) CDx assay. Both were advanced stage and were signet ring cell carcinomas with histological features comparable to those of ALK-rearranged non-small cell lung cancers. The patients were treated with conventional chemotherapy ALK fusion, one of the druggable targets in other solid tumors, is rare in gastric cancers and can be detected by comprehensive panel sequencing. Clinical studies are warranted to investigate the therapeutic response of ALK inhibitors in gastric cancers with ALK fusion.

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Section: Discussionmentioning

confidence: 79%

Two Gastric Cancers With Uncommon ALK Fusion Diagnosed With Comprehensive Panel Sequencing and Confirmed With Companion Diagnostic Assay

Kim¹,

Ahn²,

Kang

et al. 2022

AJSP: Reviews and Reports

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“…Interestingly, a novel form of ALK gene fusion was identified, being the first gastric adenocarcinoma case with RAB10-ALK fusion [40]. On the contrary, another study did not find ALK fusions by FISH and gene sequencing methods in gastric adenocarcinoma [41].…”

Section: Discussionmentioning

confidence: 98%

Kinase Inhibitor Screening Displayed ALK as a Possible Therapeutic Biomarker for Gastric Cancer

et al. 2022

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Despite advances in cancer chemotherapy, gastric cancer (GC) continues to have high recurrence rates and poor prognosis with limited treatment options. Understanding the etiology of GC and developing more effective, less harmful therapeutic approaches are vital and urgent. Therefore, this work describes a novel kinase target in malignant gastric cells as a potential therapeutic strategy. Our results demonstrate that among 147 kinase inhibitors (KI), only three molecules were significantly cytotoxic for the AGP-01 cell line. Hence, these three molecules were further characterized in their cellular mode of action. There was significant cell cycle impairment due to the expression modulation of genes such as TP53, CDKN1A, CDC25A, MYC, and CDK2 with subsequent induction of apoptosis. In fact, the Gene Ontology analysis revealed a significant enrichment of pathways related to cell cycle regulation (GO:1902749 and GO:1903047). Moreover, the three selected KIs significantly reduced cell migration and Vimentin mRNA expression after treatment. Surprisingly, the three KIs share the same target, ALK and INSR, but only the ALK gene was found to have a high expression level in the gastric cancer cell line. Additionally, lower survival rates were observed for patients with high ALK expression in TCGA-STAD analysis. In summary, we hypothesize that ALK gene overexpression can be a promising biomarker for prognosis and therapeutic management of gastric adenocarcinoma.

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“…Some other targets also showed promising clinical results in advanced GC, such as fibroblast growth factor receptor 2 ( FGFR2 ) amplification [ 167 ], epidermal growth factor receptor ( EGFR ) amplification [ 168 ], MET amplification [ 169 ], and alterations of homologous recombination deficiency–related genes [ 170 ]. In addition, there are very rare (prevalence <1%) targetable tissue–agnostic variants [ 171 ] such as BRAF V600E [ 172 ], anaplastic lymphoma kinase ( ALK ) fusion [ 173 ], and reactive oxygen species 1 ( ROS1 ) fusion [ 174 ].…”

Section: Application Of Standard Pathology Reportmentioning

confidence: 99%

A standardized pathology report for gastric cancer: 2nd edition

Park

Kook

Kim

et al. 2023

JPTM

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The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The <i>standard data elements</i> contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as <i>conditional data elements</i> to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

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Case Report: RAB10-ALK: A Novel ALK Fusion in a Patient With Gastric Cancer

Cited by 7 publications

References 9 publications

Two Gastric Cancers With Uncommon ALK Fusion Diagnosed With Comprehensive Panel Sequencing and Confirmed With Companion Diagnostic Assay

Two Gastric Cancers With Uncommon ALK Fusion Diagnosed With Comprehensive Panel Sequencing and Confirmed With Companion Diagnostic Assay

Kinase Inhibitor Screening Displayed ALK as a Possible Therapeutic Biomarker for Gastric Cancer

A standardized pathology report for gastric cancer: 2nd edition

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