Conjoined Genes as Common Events in Childhood Acute Lymphoblastic Leukemia Article Swipe
Marco Severgnini
,
Mariella D’Angiò
,
Silvia Bungaro
,
Giovanni Cazzaniga
,
Ingrid Cifola
,
Grazia Fazio
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3390/cancers14143523
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3390/cancers14143523
Acute lymphoblastic leukemia (ALL) is the most frequent childhood cancer. For the last three decades, conventional cytogenetic and molecular approaches allowed the identification of genetic abnormalities having prognostic and therapeutic relevance. Although the current cure rate in pediatric B cell acute leukemia is approximately 90%, it remains one of the leading causes of mortality in childhood. Furthermore, in the contemporary protocols, chemotherapy intensity was raised to the maximal levels of tolerability, and further improvements in the outcome will depend on the characterization and reclassification of the disease, as well as on the development of new targeted drugs. The recent technological advances in genome-wide profiling techniques have allowed the exploration of the molecular heterogeneity of this disease, even though some potentially interesting biomarkers such as conjoined genes have not been deeply investigated yet. In the present study, we performed the transcriptome sequencing (RNA-seq) of 10 pediatric B cell precursor (BCP)-ALL cases with different risk (four standard- and six high-risk patients) enrolled in the Italian AIEOP-BFM ALL2000 protocol, in order to characterize the full spectrum of transcriptional events and to identify novel potential genetic mechanisms sustaining their different early response to therapy. Total RNA was extracted from primary leukemic blasts and RNA-seq was performed by Illumina technology. Bioinformatics analysis focused on fusion transcripts, originated from either inter- or intra-chromosomal structural rearrangements. Starting from a raw list of 9001 candidate events, by employing a custom-made bioinformatics pipeline, we obtained a short list of 245 candidate fusions. Among them, 10 events were compatible with chromosomal translocations. Strikingly, 235/245 events were intra-chromosomal fusions, 229 of which involved two contiguous or overlapping genes, resulting in the so-called conjoined genes (CGs). To explore the specificity of these events in leukemia, we performed an extensive bioinformatics meta-analysis and evaluated the presence of the fusions identified in our 10 BCP-ALL cohort in several other publicly available RNA-seq datasets, including leukemic, solid tumor and normal sample collections. Overall, 14/229 (6.1%) CGs were found to be exclusively expressed in leukemic cases, suggesting an association between CGs and leukemia. Moreover, CGs were found to be common events both in standard- and high-risk BCP-ALL patients and it might be suggestive of a novel potential transcriptional regulation mechanism active in leukemic cells.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/cancers14143523
- https://www.mdpi.com/2072-6694/14/14/3523/pdf?version=1658320152
- OA Status
- gold
- Cited By
- 2
- References
- 35
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4286005725
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4286005725Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/cancers14143523Digital Object Identifier
- Title
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Conjoined Genes as Common Events in Childhood Acute Lymphoblastic LeukemiaWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-07-20Full publication date if available
- Authors
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Marco Severgnini, Mariella D’Angiò, Silvia Bungaro, Giovanni Cazzaniga, Ingrid Cifola, Grazia FazioList of authors in order
- Landing page
-
https://doi.org/10.3390/cancers14143523Publisher landing page
- PDF URL
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https://www.mdpi.com/2072-6694/14/14/3523/pdf?version=1658320152Direct link to full text PDF
- Open access
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://www.mdpi.com/2072-6694/14/14/3523/pdf?version=1658320152Direct OA link when available
- Concepts
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Transcriptome, Disease, Bioinformatics, Medicine, Tolerability, Candidate gene, Oncology, Computational biology, Gene, Biology, Genetics, Internal medicine, Gene expression, Adverse effectTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
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2025: 1, 2023: 1Per-year citation counts (last 5 years)
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35Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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