Interstitial Deletions Generating Fusion Genes

Panagopoulos, Ioannis; Heim, Sverre

doi:10.21873/cgp.20251

Cited by 12 publications

(8 citation statements)

References 350 publications

(435 reference statements)

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“…The STIL-TAL1 fusion gene has been reported in 15-25% of pediatric and young adult T-ALL cases, but much less frequently in older T-ALL patients [6]. A previous study in India found SIL-TAL1 fusion in 4/26 (15.4%) pediatric and none of the 7 adult T-ALL cases [7].…”

Section: Discussionmentioning

confidence: 96%

A Case of T-Lymphoblastic Leukemia with Submicroscopic 1p33 Deletion Resulting in STIL-TAL1 Fusion

Chang

2023

Lab Med Online

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Therefore, molecular cytogenetic diagnosis is not currently adopted for T-ALL, and no integrated tests are available to clinically identify the broad spectrum of related genes and alternative molecular mechanisms [1]. TAL1 is a classic oncogene identi ed in chromosomal translocations in acute leukemia and is an important transcription factor that forms a key regulatory circuit [4]. A submicroscopic deletion on chromosome 1p33 results in STIL-TAL1 fusion (STIL is also known as SIL), causing inappropriate overexpression of TAL1, which promotes T cell leukemogenesis [3, 4]. STIL-TAL1 fusion has been suggested to be a likely founder or truncal event, with other common genetic lesions including CDKN2A loss, PTEN mutation or loss, and NOTCH1 mutation occurring as secondary subclonal events in STIL-TAL1 positive T-ALL [5]. However, the clinical relevance and prognostic value of this rearrangement remain unclear.In this study, we identi ed STIL-TAL1 fusion in a patient with T-ALL using reverse transcriptase-polymerase chain reaction (RT-PCR) and con rmed a 1p33 deletion using chromosomal microar-

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Section: Discussionmentioning

confidence: 96%

A Case of T-Lymphoblastic Leukemia with Submicroscopic 1p33 Deletion Resulting in STIL-TAL1 Fusion

Chang

2023

Lab Med Online

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“…The deletion's exact position and extent could not be determined by Gbanding. The rationale behind our decision to examine the tumor further was that deletions sometimes generate fusion genes (33,39).…”

Section: Discussionmentioning

confidence: 99%

A Novel Cryptic t(2;3)(p21;q25) Translocation Fuses theWWTR1andPRKCEGenes in Uterine Leiomyoma With 3q- as the Sole Visible Chromosome Abnormality

Panagopoulos

Andersen

Gorunova

et al. 2022

Cancer Genomics Proteomics

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Background/Aim: Deletions in the q arm of chromosome 3 have been reported in uterine leiomyomas, also as sole anomalies. Because some neoplasia-associated deletions may give rise to tumorigenic fusion genes, we chose to investigate thoroughly one such tumor. Materials and Methods: A uterine leiomyoma obtained from a 45-year-old woman had the karyotype 46,XX,del(3)(q?) [11]. The tumor was further studied using array comparative genomic hybridization, RNA sequencing, reverse transcription polymerase chain reaction, Sanger sequencing, and fluorescence in situ hybridization methodologies. Results: The deletion was shown to be from 3q22.2 to 3q26.32. Unexpectedly, a cryptic balanced t(2;3)(p21;q25) translocation was also found affecting two otherwise normal chromosomes 2 and 3, i.e., the der(3)t(2;3) was not the deleted chromosome 3. The translocation generated two chimeras between the genes WW domain containing transcription regulator 1 (WWTR1) from 3q25.1 and protein kinase C epsilon (PRKCE) from 2p21. The WWTR1::PRKCE fusion would code for a chimeric serine/threonine kinase, whereas the reciprocal PRKCE::WWTR1 fusion would code for a chimeric transcriptional coactivator protein. Conclusion: Leiomyomas carrying a deletion on 3q may also have a balanced t(2;3)(p21;q25) leading to fusion of WWTR1 with PRKCE.Uterine leiomyomas or fibroids are the most common neoplasms found in more than 70% of women during their reproductive age and later (1, 2). In 30% to 50% of patients, the tumors may cause menorrhagia (heavy menstrual bleeding), pelvic pain/pressure, infertility and other morbidities (1) that affect the quality of life (3, 4). Uterine leiomyomas are benign monoclonal tumors (5) arising from a single myometrial stem cell that, by acquiring somatic mutations, has been transformed into a neoplastic stem cell capable of development into a leiomyoma (5-7).Cytogenetic examinations of uterine leiomyomas have revealed that 25-40% of them carry nonrandom chromosome aberrations, the most common of which is the translocation t(12;14)(q14~15;q23~24) found in 15-20% of karyotypically abnormal leiomyomas (8-27). A small number of uterine leiomyomas are cytogenetically characterized by a deletion of the q arm of chromosome 3 (10,11,15,21,22,28). We present here our molecular findings in a leiomyoma carrying a deletion on 3q. Materials and MethodsEthics statement. The study was approved by the Regional committee for medical and health research ethics. Written informed consent was obtained from the patient for publication of the case details. The ethics committee's approval included a review of the consent procedure. All patient information has been de-identified.Tumor description and Immunohistochemistry. A 45-year-old woman underwent surgery because of a clinical diagnosis of leiomyoma. The

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“…ESR1::CCDC170 fusion events are detected in approximately 8% of luminal B breast cancers, a majority of which are tandem duplications. The fusion between ESR1 and CCDC170 represents a type of intrachromosomal fusion involving genes within a 500 kb range which we coined as an adjacent gene rearrangement (AGR), which could be generated by tandem duplications, 28 interstitial deletions, 29 or cryptic balanced rearrangements. We found that these unique AGRs may appear more frequently than previously noted in breast cancer.…”

Section: Clinical and Therapeutic Relevance Of Esr1‐ccdc170‐associate...mentioning

confidence: 99%

Fusion‐associatedcarcinomas of the breast: Diagnostic, prognostic, and therapeutic significance

Loo

Yates

Yang

et al. 2022

Genes Chromosomes & Cancer

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Recurrent gene fusions comprise a class of viable genetic targets in solid tumors that have culminated several recent breakthrough cancer therapies. Their role in breast cancer, however, remains largely underappreciated due to the complexity of genomic rearrangements in breast malignancy. Just recently, we and others have identified several recurrent gene fusions in breast cancer with important clinical and biological implications. Examples of the most significant recurrent gene fusions to date include (1) ESR1::CCDC170 gene fusions in luminal B and endocrine‐resistant breast cancer that exert oncogenic function via modulating the HER2/HER3/SRC Proto‐Oncogene (SRC) complex, (2) ESR1 exon 6 fusions in metastatic disease that drive estrogen‐independent estrogen‐receptor transcriptional activity, (3) BCL2L14::ETV6 fusions in a more aggressive form of the triple‐negative subtype that prime epithelial–mesenchymal transition and endow paclitaxel resistance, (4) the ETV6::NTRK3 fusion in secretory breast carcinoma that constitutively activates NTRK3 kinase, (5) the oncogenic MYB‐NFIB fusion as a genetic driver underpinning adenoid cystic carcinomas of the breast that activates MYB Proto‐Oncogene (MYB) pathway, and (6) the NOTCH/microtubule‐associated serine–threonine (MAST) kinase gene fusions that activate NOTCH and MAST signaling. Importantly, these fusions are enriched in more aggressive and lethal breast cancer presentations and appear to confer therapeutic resistance. Thus, these gene fusions could be utilized as genetic biomarkers to identify patients who require more intensive treatment and surveillance. In addition, kinase fusions are currently being evaluated in breast cancer clinical trials and ongoing mechanistic investigation is exposing therapeutic vulnerabilities in patients with fusion‐positive disease.

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Interstitial Deletions Generating Fusion Genes

Cited by 12 publications

References 350 publications

A Case of T-Lymphoblastic Leukemia with Submicroscopic 1p33 Deletion Resulting in STIL-TAL1 Fusion

A Case of T-Lymphoblastic Leukemia with Submicroscopic 1p33 Deletion Resulting in STIL-TAL1 Fusion

A Novel Cryptic t(2;3)(p21;q25) Translocation Fuses theWWTR1andPRKCEGenes in Uterine Leiomyoma With 3q- as the Sole Visible Chromosome Abnormality

Fusion‐associatedcarcinomas of the breast: Diagnostic, prognostic, and therapeutic significance

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