Complex Genetic Evolution and Treatment Challenges in Myeloid Neoplasms: A Case of Persistent t(2;3)(p15~23;q26)/ Rearrangement, Mutation, and Transient Chimera.

Background/aim: Myelodysplastic syndromes (MDSs) are clonal bone marrow disorders characterized by ineffective hematopoiesis. They are classified based on morphology and genetic alterations, with SF3B1 variants linked to favorable prognosis and MECOM rearrangements associated with poor outcomes. The combined effects of these alterations remain unclear.

RUNX1::MIR99AHG Chimera in Acute Myeloid Leukemia.

RUNX1 fuses with over 70 different partner genes in hematological neoplasms. While common RUNX1 chimeras have been extensively studied and their prognosis is well established, our current understanding of less common RUNX1 chimeras is limited. Here, we present a case of acute myeloid leukemia (AML) with a rare RUNX1 chimera.

Accurate and comprehensive evaluation of O6-methylguanine-DNA methyltransferase promoter methylation by nanopore sequencing.

Aims: The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter region is essential in evaluating the prognosis and predicting the drug response in patients with glioblastoma. In this study, we evaluated the utility of using nanopore long-read sequencing as a method for assessing methylation levels throughout the MGMT CpG-island, compared its performance to established techniques and demonstrated its clinical applicability.

Methods: We analysed 165 samples from CNS tumours, focusing on the MGMT CpG-island using nanopore sequencing.

Fusion of Platelet Derived Growth Factor Receptor Alpha () With Ubiquitin Specific Peptidase 8 () in a Calcified Chondroid Mesenchymal Neoplasm Harboring t(4;15)(q12;q21) as a Sole Aberration.

Background/aim: The term "calcified chondroid mesenchymal neoplasm" was introduced in 2021 to describe a group of tumors characterized by various morphological features, including the formation of cartilage or chondroid matrix. These tumors frequently carry chimeric genes where the 5'-end partner gene is fibronectin 1 and the 3'-end partner gene codes for receptor tyrosine kinase. Our study explores fusion of the genes platelet-derived growth factor receptor alpha (PDGFRA) and ubiquitin-specific peptidase 8 (USP8) in calcified chondroid mesenchymal neoplasm.

Germline and Chimeras Generated by the Constitutional Translocation t(17;19)(q21;p13) in Two Siblings With Myelodysplastic Syndrome.

Background/aim: Constitutional chromosomal aberrations are rare in hematologic malignancies and their pathogenetic role is mostly poorly understood. We present a comprehensive molecular characterization of a novel constitutional chromosomal translocation found in two siblings - sisters - diagnosed with myelodysplastic syndrome (MDS).

Materials And Methods: Bone marrow and blood cells from the two patients were examined using G-banding, RNA sequencing, PCR, and Sanger sequencing.

Acute Lymphoblastic Leukemia With Near-haploid Karyotype and Philadelphia Chromosome.

Background/aim: In precursor B-cell lineage acute lymphoblastic leukemia (BCP-ALL), leukemic cells harbor genetic abnormalities that play an important role in the diagnosis, prognosis, and treatment. A subgroup of BCP-ALL is characterized by the presence of a Philadelphia (Ph) chromosome and a chimeric BCR::ABL1 gene, whereas in another subgroup, leukemic cells exhibit near-haploidy with chromosome number 24-30. This study presents the third documented case of BCP-ALL in which a near haploid clone concurrently displayed a Ph chromosome/BCR::ABL1.

Genetic Characterization of Pediatric Mixed Phenotype Acute Leukemia (MPAL).

Background/aim: Mixed phenotype acute leukemia (MPAL) is a rare hematologic malignancy in which the leukemic cells cannot be assigned to any specific lineage. The lack of well-defined, pathogenetically relevant diagnostic criteria makes the clinical handling of MPAL patients challenging. We herein report the genetic findings in bone marrow cells from two pediatric MPAL patients.

Fusion of the Genes for Interferon Regulatory Factor 2 Binding Protein 2 () and Caudal Type Homeobox 1 () in a Chondrogenic Tumor.

Background/aim: Chondrogenic tumors are benign, intermediate or malignant neoplasms showing cartilaginous differentiation. In 2012, we reported a mesenchymal chondrosarcoma carrying a t(1;5)(q42;q32) leading to an IRF2BP2::CDX1 fusion gene. Here, we report a second chondrogenic tumor carrying an IRF2BP2::CDX1 chimera.

Pathogenetic Dichotomy in Angioleiomyoma.

Background/aim: Angioleiomyoma is a benign tumor, occurs at any age, and arises most frequently in the lower extremities. Genetic information on angioleiomyomas is restricted to six reported abnormal karyotypes, losses in chromosome 22 and gains in Xq found by comparative genomic hybridization, and mutation analysis of notch receptor 2 (NOTCH2), NOTCH3, platelet-derived growth factor receptor beta (PDGFRB), and mediator complex subunit 12 (MED12) in a few tumors. Herein, we report the genetic findings in another three angioleiomyomas.

Acute Undifferentiated Leukemia With a Balanced t(5;10)(q35;p12) Resulting in Fusion of With .

Background/aim: Acute undifferentiated leukemia (AUL) is leukemia which does not express lineage-specific antigens. Such cases are rare, accounting for 2.7% of all acute leukemia.

Fusion of the High-mobility Group AT-Hook 2 () and the Gelsolin () Genes in Lipomas With t(9;12)(q33;q14) Chromosomal Translocation.

Background/aim: Lipomas are benign tumors composed of mature fat cells. They are common soft tissue tumors that often carry chromosome aberrations involving 12q14 resulting in rearrangements, deregulation, and generation of chimeras of the high-mobility group AT-hook 2 gene (HMGA2) which maps in 12q14.3.

Recurrent 8q11-13 Aberrations Leading to Rearrangements, Including Novel Chimeras and , in Lipomatous Tumors.

Background/aim: Structural abnormalities of chromosome bands 8q11-13, resulting in rearrangement of the pleomorphic adenoma gene 1 (PLAG1), are known to characterize lipoblastoma, a benign fat cell tumor, found mainly in children. Here, we describe 8q11-13 rearrangements and their molecular consequences on PLAG1 in 7 lipomatous tumors in adults.

Materials And Methods: The patients were 5 males and 2 females between 23 and 62 years old.

Genomic Complexity as a Biomarker to De-Escalate Adjuvant Imatinib Treatment in High-Risk Gastrointestinal Stromal Tumor.

Purpose: Adjuvant imatinib treatment is recommended for patients with localized gastrointestinal stromal tumor (GIST) at high risk of recurrence. Almost half of high-risk patients are cured by surgery alone, indicating a need for improved selection of patients for adjuvant therapy. The aim of this study was to investigate if genomic tumor complexity could be used as a prognostic biomarker.

Chromosome Translocation t(10;19)(q26;q13) in a CIC-sarcoma.

Background/aim: CIC-sarcomas are characterized by rearrangements of the capicua transcriptional repressor (CIC) gene on chromosome subband 19q13.2, generating chimeras in which CIC is the 5'-end partner. Most reported CIC-sarcomas have been detected using PCR amplifications together with Sanger sequencing, high throughput sequencing, and fluorescence in situ hybridization (FISH).

Novel and Fusion Genes in T-cell Acute Lymphoblastic Leukemia.

Background/aim: T-cell acute lymphoblastic leukemia (T-ALL) is a rare malignancy characterized by proliferation of early T-cell precursors that replace normal hematopoietic cells. T-ALL cells carry non-random chromosome aberrations, fusion genes, and gene mutations, often of prognostic significance. We herein report the genetic findings in cells from a T-ALL patient.

Neoplasia-associated Chromosome Translocations Resulting in Gene Truncation.

Chromosomal translocations in cancer as well as benign neoplasias typically lead to the formation of fusion genes. Such genes may encode chimeric proteins when two protein-coding regions fuse in-frame, or they may result in deregulation of genes via promoter swapping or translocation of the gene into the vicinity of a highly active regulatory element. A less studied consequence of chromosomal translocations is the fusion of two breakpoint genes resulting in an out-of-frame chimera.

Fusion of the and Genes in Uterine Leiomyoma With t(9;12)(p22;q14).

Background/aim: The translocation t(9;12) (p22;q14~15) has been reported in lipomas, pleomorphic adenomas, a myolipoma, two chondroid hamartomas, and two uterine leiomyomas. In lipomas and pleomorphic adenomas, the translocation fuses HMGA2 (12q14) with the NFIB gene from 9p22; in myolipoma, it fuses HMGA2 with C9orf92 from 9p22; and in chondroid hamartomas, fluorescence in situ hybridization (FISH) investigations showed the chromosomal aberration to cause intragenic rearrangement of HMGA2. The translocation's molecular consequence in a uterine leiomyoma is described here.

Functional temozolomide sensitivity testing of patient-specific glioblastoma stem cell cultures is predictive of clinical outcome.

Serum-free culturing of patient-derived glioblastoma biopsies enrich for glioblastoma stem cells (GSCs) and is recognized as a disease-relevant model system in glioblastoma (GBM). We hypothesized that the temozolomide (TMZ) drug sensitivity of patient-derived GSC cultures correlates to clinical sensitivity patterns and has clinical predictive value in a cohort of GBM patients. To this aim, we established 51 individual GSC cultures from surgical biopsies from both treatment-naïve primary and pretreated recurrent GBM patients.

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

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].

Fusion of High Mobility Group AT-hook 2 Gene () With the Chromosome 12 Open Reading Frame 42 Gene () in an Aggressive Angiomyxoma With del(12)(q14q23) as the Sole Cytogenetic Anomaly.

Background/aim: Aggressive angiomyxomas are mostly found in the pelvic and perineal region and are prone to recur after surgery. Cytogenetic information is available on only nine such tumors. Herein, we report the cytogenetic anomaly and its molecular consequence in another aggressive angiomyxoma.

Presence of a t(12;18)(q14;q21) Chromosome Translocation and Fusion of the Genes for High-mobility Group AT-Hook 2 () and WNT Inhibitory Factor 1 () in Infrapatellar Fat Pad Cells from a Patient With Hoffa's Disease.

Background/aim: Hoffa's disease is anterior knee pain presumably stemming from inflammatory fibrous hyperplasia of the infrapatellar fat pad (Hoffa's pad). The etiology and pathogenesis are unclear, however, and no genetic information about the disease has been published. We report the genetic findings in cells from the fat pad of a patient with Hoffa's disease.