ETV6-ACSL6 fusion gene in myeloid neoplasms: clinical spectrum, current practice, and outcomes

Wu, Xia; Cai, Hao; Qiu, Yu; Li, Jian; Zhou, Daobin; Cao, Xinxin

doi:10.1186/s13023-020-01478-6

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…Acyl-CoA synthetase long-chain family member 6 (ACSL6) is responsible for synthesizing long-chain fatty acids, and it is commonly downregulated in most types of cancers except for colorectal cancer ( 38 ). ACSL6 could be translocated with ETV6 in myeloid neoplasms, and the gene fusion might activate the oncogene near the translocated chromosomes to initiate tumorigenesis ( 39 ). Moreover, its upregulation in CRC cells promotes the synthesis of fatty acids, thus providing more energy for tumour cell proliferation ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of fatty acid metabolism-related genes in colorectal cancer and their potential implications for immunotherapy

Huang,

Sun,

Song

et al. 2023

Front. Immunol.

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IntroductionColorectal cancer is one of the most common gastrointestinal cancers and the second leading cause of cancer-related death. Although colonoscopy screening has greatly improved the early diagnosis of colorectal cancer, its recurrence and metastasis are still significant problems. Tumour cells usually have the hallmark of metabolic reprogramming, while fatty acids play important roles in energy storage, cell membrane synthesis, and signal transduction. Many pathways of fatty acid metabolism (FAM) are involved in the occurrence and development of colon cancer, and the complex molecular interaction network contains a variety of genes encoding key enzymes and related products.MethodsClinical information and RNA sequencing data were collected from TCGA and GEO databases. The prognosis model of colon cancer was constructed by LASSO-Cox regression analysis among the selected fatty acid metabolism genes with differential expression. Nomogram for the prognosis model was also constructed in order to analyze its value in evaluating the survival and clinical stage of the colon cancer patients. The differential expression of the selected genes was verified by qPCR and immunohistochemistry. GSEA and GSVA were used to analyze the enrichment pathways for high- and low-risk groups. CIBERSORT was used to analyze the immune microenvironment of colon cancer and to compare the infiltration of immune cells in the high- and low-risk groups. The “circlize” package was used to explore the correlation between the risk score signature and immunotherapy for colon cancer.ResultsWe analysed the differential expression of 704 FAM-related genes between colon tumour and normal tissue and screened 10 genes with prognostic value. Subsequently, we constructed a prognostic model for colon cancer based on eight optimal FAM genes through LASSO Cox regression analysis in the TCGA-COAD dataset, and its practicality was validated in the GSE39582 dataset. Moreover, the risk score calculated based on the prognostic model was validated as an independent prognostic factor for colon cancer patients. We further constructed a nomogram composed of the risk score signature, age and American Joint Committee on Cancer (AJCC) stage for clinical application. The colon cancer cohort was divided into high- and low-risk groups according to the optimal cut-off value, and different enrichment pathways and immune microenvironments were depicted in the groups.DiscussionSince the risk score signature was significantly correlated with the expression of immune checkpoint molecules, the prognostic model might be able to predict the immunotherapy response of colon cancer patients. In summary, our findings expand the prognostic value of FAM-related genes in colon cancer and provide evidence for their application in guiding immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of fatty acid metabolism-related genes in colorectal cancer and their potential implications for immunotherapy

Huang,

Sun,

Song

et al. 2023

Front. Immunol.

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“…The translocation t (1;12) (p36; p13) of patient 3 has previously been reported once, to the best of our knowledge, with sequencing showing an ETV6-MDS2 fusion gene lacking critical functional domains of ETV6 (downstream of exon 2) and suggesting loss of function of the translocated ETV6 allele in the corresponding AML case [ 22 ]. Patient 4 case is one of less than 20 in the literature of an ETV6-ACSL6 fusion, with all cases presenting myeloproliferative neoplasm with eosinophilia, a trait that could be related to aberrant induction, from the ETV6 5′ region, of the IL-3 gene located not far from the 5q31 breakpoint [ 23 – 25 ]; ACSL6 itself codes under normal circumstances for an acyl-CoA synthetase [ 26 ]. In our patient, it is plausible to hypothesize that the NPM1 mutation had been a late subclonal event leading to transformation of the myeloproliferative neoplasm.…”

Section: Discussionmentioning

confidence: 99%

Description of an Institutional Cohort of Myeloid Neoplasms Carrying ETV6-Locus Deletions or ETV6 Rearrangements

Papadopoulou¹,

Schoumans²,

Scarpelli³

et al. 2023

Acta Haematol

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The gene encoding for transcription factor ETV6 presents recurrent lesions in hematologic neoplasms, most notably the ETV6-RUNX1 rearrangement in childhood B-ALL. The role of ETV6 for normal hematopoiesis is unknown, but loss of its function probably participates in oncogenic procedures. In myeloid neoplasms, ETV6-locus (12p13) deletions are rare but recurrent; ETV6 translocations are even rarer, but those reported seem to have phenotype-defining consequences. We herein describe the genetic and hematologic profile of myeloid neoplasms with ETV6 deletions (10 cases), or translocations (4 cases) diagnosed in the last ten years in our institution. We find complex karyotype to be the most prevalent one among patients with 12p13 deletion (8/10 patients), with most frequent coexisting anomalies being monosomy 7 or deletion 7q32 (5/10), monosomy 5 or del5q14-15 (5/10) and deletion/inversion of chromosome 20 (5/10), and most frequent point-mutation being TP53 mutation (6/10 patients). Mechanisms of synergy of these lesions are unknown. We describe the entire genetic profile and hematologic phenotype of cases with extremely rare ETV6 translocations, confirming the biphenotypic T/myeloid nature of acute leukemia associated to ETV6-NCOA2 rearrangement, the association of t (1;12) (p36;p13) and of the CHIC2-ETV6 fusion with MDS/AML, and the association of the ETV6-ACSL6 rearrangement with myeloproliferative neoplasm with eosinophilia. Mutation of the intact ETV6 allele was present in two cases and seems to be subclonal to the chromosomal lesions. Decoding the mechanisms of disease related to ETV6 haploinsufficiency or rearrangements is important for the understanding of pathogenesis of myeloid neoplasms and fundamental research must be guided by observational cues.

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“…The PDGFRB gene is located in the 5q22, which encodes platelet-derived growth factor cell surface receptors. So far, more than 40 PDGFRB associated fusion genes have been found [5]. T (5;12) (q31-q33; p12) is a common chromosomal aberration, and ETV6 is the most common fusion gene [6].…”

Section: Discussionmentioning

confidence: 99%

A Novel WNK1-PDGFRB Fusion Gene in Myeloid Neoplasm With Eosinophilia: A Case Report With a Literature Review

Wang

Cao

Lin

et al. 2022

Preprint

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Platelet-derived growth factor receptor beta (PDGFRB) rearrangements play an important role in the pathogenesis of eosinophilia-associated myeloid/lymphoid neoplasms. Here, a novel WNK1-PDGFRB fusion gene has been identified in myeloid neoplasm with eosinophilia by RNA-sequencing. This is the first study that reported on the WNK1-PDGFRB fusion gene expression in myeloid neoplasm with eosinophilia. In addition, the WNK1-PDGFRB fusion retained the entire kinase domain of PDGFRB and response to imatinib at low concentration.

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ETV6-ACSL6 fusion gene in myeloid neoplasms: clinical spectrum, current practice, and outcomes

Cited by 7 publications

References 22 publications

Prognostic value of fatty acid metabolism-related genes in colorectal cancer and their potential implications for immunotherapy

Prognostic value of fatty acid metabolism-related genes in colorectal cancer and their potential implications for immunotherapy

Description of an Institutional Cohort of Myeloid Neoplasms Carrying ETV6-Locus Deletions or ETV6 Rearrangements

A Novel WNK1-PDGFRB Fusion Gene in Myeloid Neoplasm With Eosinophilia: A Case Report With a Literature Review

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