RNA Sequencing of Primary Cutaneous and Breast-Implant Associated Anaplastic Large Cell Lymphomas Reveals Infrequent Fusion Transcripts and Upregulation of PI3K/AKT Signaling via Neurotrophin Pathway Genes.
Simple Summary: Cutaneous and breast implant-associated anaplastic large-cell lymphomas are usually localized neoplasms with an indolent clinical course compared to systemic ALCL. However comparative analyses of the molecular features of these two entities have not yet been reported. We performed ta...
| Publicado en: | Cancers Vol. 13; no. 24; pp. 6174 - 6175 |
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| Autores principales: | , , , , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
MDPI
Dec2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=154348907&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 154348907 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Dec2021 vid: 13 iid: 24 pid: 97109 pub: MDPI artinfo: ui: 154348907 154348907 154348907 10.3390/cancers13246174 154348907 ppf: 6174 ppct: 1 formats: tig: atl: RNA Sequencing of Primary Cutaneous and Breast-Implant Associated Anaplastic Large Cell Lymphomas Reveals Infrequent Fusion Transcripts and Upregulation of PI3K/AKT Signaling via Neurotrophin Pathway Genes. aug: au: Di Napoli, Arianna Vacca, Davide Bertolazzi, Giorgio Lopez, Gianluca Piane, Maria Germani, Aldo Rogges, Evelina Pepe, Giuseppina Santanelli Di Pompeo, Fabio Salgarello, Marzia Jobanputra, Vaidehi Hsiao, Susan Wrzeszczynski, Kazimierz O. Berti, Emilio Bhagat, Govind affil: Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, 00189 Rome, Italy sug: subj: RNA Sequence Analysis Breast Implants Lymphoma, T-Cell Phosphotransferases Signal Transduction Nerve Growth Factors Human Gene Expression Profiling Gene Rearrangement Karyotyping Genomics Nuclear Proteins ab: Simple Summary: Cutaneous and breast implant-associated anaplastic large-cell lymphomas are usually localized neoplasms with an indolent clinical course compared to systemic ALCL. However comparative analyses of the molecular features of these two entities have not yet been reported. We performed targeted RNA sequencing, which revealed that fusion transcripts, although infrequent, might represent additional pathogenetic events in both diseases. We also found that these entities display upregulation of the PI3K/Akt pathway and show enrichment in genes of the neurotrophin signaling pathway. These findings advance our knowledge regarding the pathobiology of cALCL and BI-ALCL and point to additional therapeutic targets. Cutaneous and breast implant-associated anaplastic large-cell lymphomas (cALCLs and BI-ALCLs) are two localized forms of peripheral T-cell lymphomas (PTCLs) that are recognized as distinct entities within the family of ALCL. JAK-STAT signaling is a common feature of all ALCL subtypes, whereas DUSP22/IRF4, TP63 and TYK gene rearrangements have been reported in a proportion of ALK-negative sALCLs and cALCLs. Both cALCLs and BI-ALCLs differ in their gene expression profiles compared to PTCLs; however, a direct comparison of the genomic alterations and transcriptomes of these two entities is lacking. By performing RNA sequencing of 1385 genes (TruSight RNA Pan-Cancer, Illumina) in 12 cALCLs, 10 BI-ALCLs and two anaplastic lymphoma kinase (ALK)-positive sALCLs, we identified the previously reported TYK2-NPM1 fusion in 1 cALCL (1/12, 8%), and four new intrachromosomal gene fusions in 2 BI-ALCLs (2/10, 20%) involving genes on chromosome 1 (EPS15-GNG12 and ARNT-GOLPH3L) and on chromosome 17 (MYO18A-GIT1 and NF1-GOSR1). One of the two BI-ALCL samples showed a complex karyotype, raising the possibility that genomic instability may be responsible for intra-chromosomal fusions in BI-ALCL. Moreover, transcriptional analysis revealed similar upregulation of the PI3K/Akt pathway, associated with enrichment in the expression of neurotrophin signaling genes, which was more conspicuous in BI-ALCL, as well as differences, i.e., over-expression of genes involved in the RNA polymerase II transcription program in BI-ALCL and of the RNA splicing/processing program in cALCL. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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