Unraveling the Genetic Heterogeneity of Acute Lymphoblastic Leukemia Based on NGS Applications DOI Open Access

V. Maldonado,

J. Acosta, Irene Marcos

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(23), P. 3965 - 3965

Published: Nov. 26, 2024

Acute lymphoblastic leukemia (ALL) is a hematological neoplasm characterized by the clonal expansion of abnormal lymphoid precursors in bone marrow, which leads to alterations processes cell differentiation and maturation as consequence genetic alterations. The integration conventional methods, such cytogenetics immunophenotyping, next-generation sequencing (NGS) has led significant improvements at diagnosis patient stratification; this also allowed discovery several novel molecular entities with specific variants that may drive leukemogenesis. Nevertheless, understanding process leukemogenesis remains challenge since disease persists most frequent cancer children; it accounts for approximately one-quarter adult acute leukemias, management take into consideration high intra- inter-tumor heterogeneity relapse risk due various events can occur during evolution. Some germline have been identified factors or found be related response treatment. Therefore, better knowledge B-ALL will prognostic impact from perspective personalized medicine. This review aims compare, synthesize, highlight recent findings concerning ALL obtained through NGS new subtypes based on immunophenotypic characteristics, mutational profiles, expression profiles.

Language: Английский

The Role of Chronic Inflammation in Pediatric Cancer DOI Open Access

Christine Mella,

Panogiotis Tsarouhas,

Maximillian Brockwell

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(1), P. 154 - 154

Published: Jan. 6, 2025

Inflammation plays a crucial role in wound healing and the host immune response following pathogenic invasion. However, unresolved chronic inflammation can result tissue fibrosis genetic alterations that contribute to pathogenesis of human diseases such as cancer. Recent scientific advancements exploring underlying mechanisms malignant cellular transformations cancer progression have exposed significant disparities between pediatric adult-onset cancers. For instance, cancers tend lower mutational burdens arise actively developing tissues, where cell-cycle dysregulation leads gene, chromosomal, fusion gene development not seen counterparts. As such, findings adult cannot be directly applied cancers, unique mutations inherent etiologies remain poorly understood. Here, we review processes chromosomal instability, tumor microenvironment, tumorigenesis transformation explore current therapeutic interventions maintain and/or restore inflammatory homeostasis.

Language: Английский

Citations

3
A single-cell sequencing-based analysis of a 13-year-old with maxillary sinus NUT carcinoma DOI
Zhuomiao Ye, Xin Li, Fei Xie

et al.

Oral Oncology, Journal Year: 2025, Volume and Issue: 162, P. 107185 - 107185

Published: Jan. 24, 2025

Language: Английский

Citations

0
The expanding universe of NUTM1 fusions in pediatric cancer DOI Creative Commons
Rosane Charlab, Rebecca Racz

Clinical and Translational Science, Journal Year: 2023, Volume and Issue: 16(8), P. 1331 - 1339

Published: April 21, 2023

NUT midline carcinoma family member 1 (NUTM1) fusions were originally identified in poorly differentiated and clinically aggressive carcinomas typically located the structures of children young adults, collectively known as (midline) carcinomas. Next-generation sequencing later uncovered NUTM1 a variety other pediatric adult cancers diverse location type, including hematologic malignancies, cutaneous adnexal tumors, sarcomas. A vast array with bromodomain containing 4 (BRD4) or 3 (BRD3), which are characteristic carcinoma, several fusion partners have been associated variable prognosis. These non-kinase thought to cause epigenetic reprogramming, thereby promoting proliferation, hindering differentiation cancer cells. Many questions about both function naïve protein, is mostly restricted germ cells testis related spermatogenesis oncogenic mechanisms various cancer, still unanswered. Moreover, whether there relationship defined by presence between conventional NUTM1-rearranged neoplasms remains be elucidated. This review will focus on recent discoveries found cancers, their prognostic impact, emergence novel drivers.

Language: Английский

Citations

9
Prenatal origin of NUTM1 gene rearrangement in infant B‐cell precursor acute lymphoblastic leukaemia DOI
Michela Bardini, Grazia Fazio,

L Corral Abascal

et al.

British Journal of Haematology, Journal Year: 2024, Volume and Issue: 205(5), P. 1883 - 1888

Published: Aug. 5, 2024

Rearrangement of NUTM1 gene (NUTM1r) is one the most frequent aberrations occurring in infants (younger than 1 year at diagnosis) with B-cell precursor Acute Lymphoblastic Leukaemia (BCP-ALL). In this study we had unique opportunity to analyze umbilical cord blood (UCB) sample from infant patient NUTM1r BCP-ALL. Herein reported for first time that ALL arise prenatally, as both patient-specific CUX1::NUTM1 fusion gene, well two IG/TR leukaemic markers were already present and detectable patient's UCB birth. Our results clearly demonstrate prenatal origin

Language: Английский

Citations

2
Molecularly Defined Thoracic Neoplasms DOI
Anja C. Roden

Advances in Anatomic Pathology, Journal Year: 2024, Volume and Issue: 31(5), P. 303 - 317

Published: March 19, 2024

Molecularly defined neoplasms are increasingly recognized, given the broader application and performance of molecular studies. These studies allow us to better characterize these learn about their pathogenesis. In thorax, molecularly include tumors such as NUT carcinoma, SMARCA4-deficient undifferentiated tumor (DUT), primary pulmonary myxoid sarcoma with EWSR1::CREB1 fusion, hyalinizing clear cell SMARCB1-deficient neoplasms. Overall, rare but now more often recognized widely available immunostains (NUT carcinoma), BRG1 (SMARCA4-DUT), INI-1 (SMARCB1-deficient neoplasm). Furthermore, cytogenetic for EWSR1 support a carcinoma or are, in general, easily accessible. This enables pathologists recognize diagnose tumors. The diagnosis is important clinical management treatment. For instance, trials patients SMARCA4-DUT, SMACRB1-deficient Herein, our current knowledge clinical, morphologic, immunophenotypic, features carcinomas, sarcomas, will be reviewed.

Language: Английский

Citations

1
Nuclear protein in testis (NUT) midline carcinoma of the larynx: A rare case report of a paediatric patient and literature review DOI
Gamze Uğurluer, Nazmiye Dinçer, Ayça Erşen Danyeli

et al.

Cancer/Radiothérapie, Journal Year: 2024, Volume and Issue: 28(4), P. 385 - 389

Published: Aug. 1, 2024

Language: Английский

Citations

1
The Role of Gene Fusions in Thymic Epithelial Tumors DOI Open Access
Anja C. Roden

Cancers, Journal Year: 2023, Volume and Issue: 15(23), P. 5596 - 5596

Published: Nov. 27, 2023

Thymic epithelial tumors (TET) are rare and large molecular studies therefore difficult to perform. However, institutional case series multi-institutional have identified a number of interesting aberrations in TET, including gene fusions subset these tumors. These can aid the diagnosis, shed light on pathogenesis tumors, potentially may provide patients with opportunity undergo targeted therapy or participation clinical trials. Gene that been TET include MAML2 rearrangements 50% 56% mucoepidermoid carcinomas (MAML2::CRTC1), 77% 100% metaplastic thymomas (YAP1::MAML2), 6% B2 B3 (MAML2::KMT2A); NUTM1 NUT (most commonly BRD4::NUTM1); EWSR1 rearrangement hyalinizing clear cell carcinoma (EWSR1::ATF1); NTRK thymoma (EIF4B::NTRK3). This review focuses which fusion genes identified, their morphologic, immunophenotypic, characteristics potential implications genes. Larger, multi-institutional, global needed further elucidate but sometimes very aggressive order optimize patient management, participate trials,

Language: Английский

Citations

2
NSD3::NUTM1 Fusion Sarcoma Mimicking Malignant Peripheral Nerve Sheath Tumor with Prolonged Survival DOI Creative Commons
Jing Di,

Ali M. Alhaidary,

Chi Wang

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1709 - 1709

Published: Aug. 1, 2024

Nuclear Protein in Testis (NUT)-rearranged tumors comprise predominantly NUT carcinoma but also include certain lymphomas, leukemias, skin appendage tumors, and sarcomas. Although histologically diverse, all are genetically identified by oncogenic rearrangement the NUTM1 gene. Many fusion partners occur, NSD3 is carcinoma's third most common partner. Herein, we present a case of 26-year-old man with an

Language: Английский

Citations

0
Unraveling the Genetic Heterogeneity of Acute Lymphoblastic Leukemia Based on NGS Applications DOI Open Access

V. Maldonado,

J. Acosta, Irene Marcos

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(23), P. 3965 - 3965

Published: Nov. 26, 2024

Acute lymphoblastic leukemia (ALL) is a hematological neoplasm characterized by the clonal expansion of abnormal lymphoid precursors in bone marrow, which leads to alterations processes cell differentiation and maturation as consequence genetic alterations. The integration conventional methods, such cytogenetics immunophenotyping, next-generation sequencing (NGS) has led significant improvements at diagnosis patient stratification; this also allowed discovery several novel molecular entities with specific variants that may drive leukemogenesis. Nevertheless, understanding process leukemogenesis remains challenge since disease persists most frequent cancer children; it accounts for approximately one-quarter adult acute leukemias, management take into consideration high intra- inter-tumor heterogeneity relapse risk due various events can occur during evolution. Some germline have been identified factors or found be related response treatment. Therefore, better knowledge B-ALL will prognostic impact from perspective personalized medicine. This review aims compare, synthesize, highlight recent findings concerning ALL obtained through NGS new subtypes based on immunophenotypic characteristics, mutational profiles, expression profiles.

Language: Английский

Citations

0