Identification of a novel partner gene, <i>KIAA1217</i>, fused to <i>RET</i>: Functional characterization and inhibitor sensitivity of two isoforms in lung adenocarcinoma

Lee, Mi-Sook; Kim, Ryong Nam; Hoseok, I; Oh, Doo‐Yi; Song, Ji-Young; Noh, Ka-Won; Kim, Yujin; Yang, Jung Wook; Lira, Maruja E.; Lee, Chang-Hun; Lee, Min Ki; Kim, Yeoung Dae; Mao, Mao; Han, Joungho; Kim, Young Tae; Choi, Yoon‐La

doi:10.18632/oncotarget.9137

Cited by 32 publications

(26 citation statements)

References 41 publications

(59 reference statements)

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“…KIAA1217 has not been well described, but encodes a sickle tail protein homologue and is highly expressed, particularly in intervertebral discs 29 . KIAA1217–RET fusion, as seen in our patient 5, has been previously reported in lung adenocarcinoma, 31,32 but not previously in a mesenchymal neoplasm. CLIP2–RET fusion, seen in the kidney tumour from our patient 3, was reported only once previously, in a chest wall tumour with IFS‐like morphology from a 2‐month‐old male 20 .…”

Section: Discussionsupporting

confidence: 75%

Recurrent RET gene fusions in paediatric spindle mesenchymal neoplasms*

et al. 2020

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Aims: The classification of paediatric spindle mesenchymal tumours is evolving, and the spectrum of socalled 'infantile fibrosarcoma' has expanded to include tumours with NTRK, BRAF and MET gene fusions. RETrearranged paediatric spindle cell neoplasms are an emerging group; there is sparse literature on their clinical, pathological and genetic features, and their nosological place in the canon of soft tissue tumours is uncertain. In this study, we report five RET-rearranged paediatric spindle cell tumours with fusion partners MYH10, KIAA1217 and CLIP2. Methods and results: The tumours occurred in the pelvic region, paraspinal region, kidney and subcutaneous tissue of hand and abdomen. The patients' ages ranged from 6 months to 13 years (median 1 year). The tumours were composed of monomorphic spindle cells arranged in a fascicular pattern. Lesional cells had minimally atypical ovoid or tapered nuclei and pale cytoplasm with indistinct borders. Necrosis was not identified. Mitoses numbered three to 12 per 10 high-power field. Cases showed inconsistent and variable expression of S100, CD34 and SMA. Clinical behaviour ranged from small lesions potentially cured by simple resection to large lesions exhibiting metastasis, but responsive to kinase inhibitor therapy. Conclusions: Our findings help to define RET-rearranged spindle cell tumours. Although it is likely that these tumours comprise part of the morphological and clinical spectrum of infantile fibrosarcoma (IFS), identification of RET gene alteration is important for its unique therapeutic implications.

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Section: Discussionsupporting

confidence: 75%

Recurrent RET gene fusions in paediatric spindle mesenchymal neoplasms*

et al. 2020

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“…It was recently discovered as a novel fusion partner gene with the RET protooncogene in one case of lung adenocarcinoma, whereby the fusion of RET with KIAA1217 led to activation of downstream signalling molecules: STAT3, AKT, and ERK. This was linked with increased tumour cell invasion in the study [23]. However, there are no further studies or reports of this protein in carcinoma progression.…”

Section: Proteomic Comparisonsmentioning

confidence: 72%

Label-free tissue proteomics can classify oral squamous cell carcinoma from healthy tissue in a stage-specific manner

et al. 2018

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No prognostic or predictive biomarkers for oral squamous cell carcinoma (OSCC) exist. We aimed to discover novel proteins, altered in OSCC, to be further investigated as potential biomarkers, and to improve understanding about pathways involved in OSCC. Materials and Methods: Proteomic signatures of seven paired healthy and OSCC tissue samples were identified using ultra-definition quantitative mass spectrometry, then analysed and compared using Anova, principal component analysis, hierarchical clustering and OPLS-DA modelling. A selection of significant proteins that were also altered in the serum from a previous study (PMID: 28632724) were validated immunohistochemically on an independent cohort (n = 66) to confirm immunopositivity and location within tumour tissue. Ingenuity Pathways Analysis was employed to identify altered pathways. Results: Of 829 proteins quantified, 257 were significant and 72 were able to classify healthy vs OSCC using OPLS-DA modelling. We identified 19 proteins not previously known to be upregulated in OSCC, including prosaposin and alpha-taxilin. KIAA1217 and NDRG1 were upregulated in stage IVa compared with stage I tumours. Altered pathways included calcium signalling, cellular movement, haematological system development and function, and immune cell trafficking, and involved NF-kB and MAPK networks. Conclusions: We found a set of proteins reliably separating OSCC tumour from healthy tissue, and multiple proteins differing between stage I and stage IVa OSCC. These potential biomarkers can be studied and validated in larger cohorts.

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“…This suggests an important function of stromal reprogramming in destabilization of epithelial differentiation and integrity. For module yellow, which is progressively up--regulated from normal stroma to adenoma to mCA, the top candidate hub genes consisted of CDH1, ST14, EHF, KRT8, and KIAA1217, all of which have important roles in epithelial cells, and/or are associated with tumour malignancy (Lee et al, 2016;Moll et al, 2008;Uhland, 2006;Yamazaki et al, 2015). Similarly, hub genes of module brown, COL8A2, SORCS2, BGN, RUNX1, and IGFBP2, displayed a progressive increase from normal stroma to CAS in adenoma and mCA.…”

Section: Results Transcriptomic Profiling Of Matched Cas and Normal Smentioning

confidence: 99%

Differential stromal reprogramming in benign and malignant naturally occurring canine mammary tumours identifies disease-promoting stromal components

Amini

Nassiri

Malbon

et al. 2019

Preprint

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statement: RNAsequencing--based analysis of stromal reprogramming between benign and malignant naturally occurring canine mammary tumours identifies potential molecular drivers in cancer--associated stroma that support tumour growth and malignancy. AbstractThe importance of cancer--associated stroma (CAS) for initiation and progression of cancer is well accepted. However, as stromal changes in benign forms of naturally occurring tumours are poorly understood, it remains unclear how CAS from benign and malignant tumours compare. Spontaneous canine mammary tumours are viewed as excellent models of human mammary carcinomas (mCA). We have recently reported highly conserved stromal reprogramming between canine and human mCA based on transcriptome analysis of laser--capture-microdissected FFPE specimen. To identify stromal changes between benign and malignant mammary tumours, we have analysed CAS and matched normal stroma from 13 canine mammary adenomas and compared them to 15 canine mCA. Our analyses revealed distinct stromal reprogramming even in small benign tumours. While similarities in stromal reprogramming exist, the CAS signature clearly distinguished adenomas from mCA, suggesting that it may reliably discriminate between benign and malignant tumours. We identified strongly discriminatory genes and found strong differential enrichment in several hallmark signalling pathways between benign and malignant CAS. The distinction between CAS from adenoma and mCA was further substantiated by differential abundance in cellular composition. Finally, to determine key players in CAS reprograming between adenomas and mCA, a network--based gene screening method identified modules of co--expressing genes with distinct expression profile in benign and malignant CAS, and revealed several hub genes as potential molecular drivers in CAS. Given the relevance of canine CAS as a model for the human disease, our

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Identification of a novel partner gene, KIAA1217, fused to RET: Functional characterization and inhibitor sensitivity of two isoforms in lung adenocarcinoma

Cited by 32 publications

References 41 publications

Recurrent RET gene fusions in paediatric spindle mesenchymal neoplasms*

Recurrent RET gene fusions in paediatric spindle mesenchymal neoplasms*

Label-free tissue proteomics can classify oral squamous cell carcinoma from healthy tissue in a stage-specific manner

Differential stromal reprogramming in benign and malignant naturally occurring canine mammary tumours identifies disease-promoting stromal components

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