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PubMed2026

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

Humans↗
PubMed2026

Liquid biopsy: a new window on the BRCA genes.

The Breast Cancer Susceptibility Gene (BRCA)-associated tumors represent a constantly evolving and intriguing scenario in oncology, in which the availability of novel systemic treatment, mainly including the poly (ADP-ribose) polymerase (PARP) inhibitors, has enabled an improved survival benefit in clinical subgroups. The expanding regulatory approvals of PARP inhibitors have inevitably reshaped the clinical indications for BRCA testing, moving the BRCA1/2 profiling from the traditional and preventive workflows to therapeutic paths. Despite advances in technology and treatment, substantial limitations remain in current genetic and genomic tools for the detection of deleterious BRCA1/2 variants. Germline and tumor tissue testing provide only a snapshot of a patient's disease, failing to capture the dynamic and longitudinal aspects of tumor clonal evolution. In this scenario, liquid biopsy (LB) profiling of BRCA1/2 genes, primarily as circulating tumor DNA, represents a highly active area of research potentially affecting many aspects of cancer screening, diagnosis, and monitoring in individuals who are carriers of BRCA1/2 deleterious variants. Beyond the attractive potential to surrogate the tumor tissue testing, to overcome the cancer spatial and temporal heterogeneity, and to monitor the tumor mutational profile over time, accurately detecting all clinically relevant BRCA genetic variants and epigenetic modifications using LB remains technically challenging.

BRCA1/2↗
PubMed2026

Structural complexity and mechanistic diversity of MECOM rearrangements in myeloid neoplasms.

Rearrangements involving MECOM at chromosome 3q26.2 are recurrent in myeloid neoplasms, classically represented by inv(3)(q21q26.2) and t(3;3)(q21;q26.2), which reposition the GATA2-distal haematopoietic enhancer and drive aberrant EVI1 overexpression. However, the full structural and mechanistic diversity of MECOM rearrangements (MECOM-r) is yet to be explored. We retrospectively analysed 97 cases with cytogenetically defined MECOM-r and identified 12 with complex rearrangements using GTG-banded karyotyping and tri-colour interphase/metaphase fluorescence in situ hybridisation analyses. These 12 cases demonstrated remarkable structural heterogeneity. The abnormalities encompassed translocations, inversions, insertions, duplications, and deletions, which often coexisted within the same specimen as multiple rearranged subclones. Insertional events emerged as a distinct mechanism of MECOM activation. These encompassed insertions of MYNN and/or MECOM into chromosomes 1 and 6, insertion of chromosome 8 segment into MECOM, and inverted insertions between homologous chromosome 3 segments. Recurrent breakpoints at 3q21 across multiple cases, together with localised copy number imbalances frequently involving the MYNN and GOLIM4 loci at 3q26.2, underscore the architectural fragility of these two regions. Co-occurring abnormalities such as -5/del(5q), -7/del(7q), and TP53 loss were common, reflecting a permissive genomic background for chromosomal reassembly. Our findings expand the mechanistic landscape of MECOM-r beyond canonical inv(3)/t(3;3), establishing 3q21 and 3q26.2 as structural 'hotspots' and genomic instability hubs. Distinct from fusion-driven oncogenes such as KMT2A, MECOM activation results from enhancer hijacking and regional structural remodelling, leading to EVI1 overexpression and clonal evolution in myeloid malignancies.

Humans↗
PubMed2026

Integrated morphologic, immunophenotypic, and molecular profiling of advanced upper tract urothelial carcinoma across tumor compartments supports biopsy-based testing.

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with limited molecular characterization in advanced disease. FGFR3 alterations are well established in low-grade urothelial carcinoma, but their prevalence, stability, and biological significance in locally advanced and metastatic UTUC remain only partially defined. We performed an integrated morphologic, immunohistochemical, and molecular analysis of 24 locally advanced and/or metastatic UTUC from 20 patients. FGFR3 status was assessed by RT-PCR across multiple tumor compartments, including biopsies, primary tumors, lymph-node metastases, and distant metastatic sites. Immunohistochemistry included CK20, CK5, GATA3, p53, and mismatch repair proteins. Targeted next-generation sequencing (NGS) was used to characterize co-occurring genomic alterations and to assess concordance with p53 immunophenotype. FGFR3 alterations were identified in 50% of patients and in 54.2% of analyzed tumors. FGFR3 status showed high intra-patient stability, with concordance between primary tumors and distant metastases in 90% of cases, whereas concordance with lymph node metastases was lower (50%), suggesting site-specific clonal divergence. Despite advanced stage, 92.3% of FGFR3-altered tumors displayed papillary urothelial carcinoma morphology, and most showed a luminal immunophenotype (61.5% by CK20/CK5 and 69.2% by GATA3/CK5). Targeted NGS revealed additional pathogenic alterations in 75% of patients, most frequently involving RTK/RAS/MAPK signaling (70%), cell-cycle regulation (25%), and PI3K/AKT pathway components (10%). TP53 mutations co-occurred with FGFR3 alterations in 60% of FGFR3-mutated patients and showed 90.4% concordance with p53 immunohistochemistry. Finally, a few cases exhibited complex, multi-site FGFR3 mutational patterns, consistent with intratumoral clonal evolutions. In conclusion, FGFR3 alterations are frequent and remarkably stable in advanced UTUC, even in high-grade and metastatic disease. These findings support the reliability of FGFR3 testing on limited diagnostic material and reinforce its relevance for therapeutic stratification. UTUC emerges as a molecularly dynamic disease in which early oncogenic drivers such as FGFR3 continue to shape tumor biology and therapeutic vulnerability at advanced stages.

Humans↗
PubMed1977

Paroxysmal nocturnal hemoglobinuria (PNH) as a clonal disorder.

1. Clonal theories of disease, particularly progressive clonal growth and selection in tumorogenesis, were briefly cited. 2. Evidence for the clonal nature of PNH was presented. Correlation of red cell hemolysis with (a) G-6-PD type in two female G-6-PD mosaics with PNH and with (b) erythrocyte acetylcholinesterase deficiency, provides strong evidence for the clonal theory of PNH. 3. Possible pitfalls in defining "hidden PNH clones" in other diseases by the use of PNH hemolytic tests were discussed. 4. The potential of PNH as a study model for clonal evolution in human disease was emphasized.

Acetylcholinesterase↗
PubMed2026

Selective Inhibition of DNA Polymerase Proofreading: A Metabolic-Fidelity Mechanism Explains Agent Orange-Associated Myelodysplasia.

We performed a focused review to better understand the pathogenesis of Agent Orange (AO)-associated myelodysplastic syndrome (MDS). We first examined the mechanisms underlying conventional (de novo) MDS, a clonal hematopoietic neoplasm that typically develops in later life, and integrated these findings with our recent analysis of obesity-associated carcinogenesis. Accordingly, we propose that genomic instability in de novo MDS results from selective inhibition of the DNA polymerase proofreading exonuclease. In obesity-associated carcinogenesis, impaired AMP-activated protein kinase (AMPK) activity disrupts mitochondrial ATP production, increasing intracellular AMP concentrations. Elevated AMP selectively inhibits the proofreading exonuclease while preserving polymerase activity, allowing replication errors to escape correction and become fixed as somatic mutations. Molecular studies demonstrate that AO-associated MDS exhibits essentially the same mutational profile as de novo disease despite arising after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in young, otherwise healthy military personnel. Because TCDD is highly lipophilic, it accumulates in adipose tissue and is released slowly over decades, producing sustained mitochondrial dysfunction, reduced ATP synthesis, and chronic elevation of intracellular AMP. We propose that this metabolic disturbance converges on the same endpoint-selective inhibition of the proofreading exonuclease-thereby promoting mutagenesis and clonal evolution. Recent studies further strengthen the central role of proofreading by demonstrating that many mutations, including many found in MDS, previously attributed to spontaneous cytosine deamination, instead arise from DNA polymerase misincorporation of thymidine opposite cytosine, particularly at CpG dinucleotides, emphasizing the critical importance of fully active proofreading in preventing such misincorporations from accumulating as mutations in the genome of the cell.

AMP↗
PubMed2026

Integrating Radiogenomics and CSF-Based Liquid Biopsy Sequencing for Precision Neuro-Oncology.

Glioblastoma and diffuse gliomas pose major therapeutic challenges due to marked intratumoral heterogeneity, limited tissue accessibility, and the blood-brain barrier. Tissue-based next-generation sequencing (NGS) remains essential for WHO CNS5 molecular classification, yet it is invasive and poorly suited to serial monitoring. Two complementary non- or minimally invasive approaches have advanced rapidly: radiogenomics, which correlates multiparametric MRI features with genomic alterations, and cerebrospinal fluid (CSF) liquid biopsy sequencing, which detects circulating tumor DNA with high tissue concordance. This review examines the independent progress and synergistic integration of radiogenomics and CSF-NGS. Imaging signatures can non-invasively predict key drivers (IDH1/2, EGFR, TERT, PTEN, TP53) and molecular subtypes, while CSF-ctDNA sequencing enables real-time assessment of clonal evolution, therapy resistance (including post-temozolomide hypermutation), and residual disease. We discuss technical considerations, performance metrics, multimodal artificial-intelligence fusion, and emerging clinical applications for diagnosis, prognosis, treatment selection, and longitudinal surveillance. Critical challenges, standardization, prospective validation, and workflow integration are highlighted. By combining the spatial phenotypic information of radiogenomics with the temporal genomic resolution of CSF sequencing, this multimodal strategy offers a promising path toward precision neuro-oncology and reduced reliance on repeated invasive sampling.

Humans↗
PubMed1978

Comparative cytogenetic studies of normal and leukemic lymphoblastoid cell lines during the course of their establishment.

A comparative chromosomal analysis was made of 10 human lymphoblastoid cell lines, four of which originated from normal donor lymphocytes and six of which were from leukemic peripheral blood. For comparison of lymphoblastoid cells with respect to their normal or leukemic origin, cytogenetic studies have been carried out regularly since the beginning of the culture during more than 3 years. Samples were drawn during the three phases previously described for the establishment of these lines. The chromosome distribution remained diploid for at least 2 years in normal cell lines, and the cells were euploid. In contrast, an important variability of the chromosome set was demonstrated during the same period in leukemic cell lines. Moreover, in these lines, it was always possible to observe a nonsystemic pseudodiploidy. After 2 years, a clonal evolution was described in both types of cell lines that carried at least one marker. With a controlled-heating denaturation technique, it was possible to identify the markers as specific to each cell line. The cells with marker chromosomes appeared to have a selective advantage of growth.

Aneuploidy↗
PubMed1979

[Chromosome abnormalities in malignant lymphoma].

Analysis of the karyotype from bone marrow tissue and lymphocyte culture of the peripheral blood was performed in 25 children either with Hodgkin's or non-Hodgkins' lymphoma prior to any treatment. numeric aberrations were confirmed in 40% of the patients; in these the hyperdiploid number of chromosomes ranged from 52 to 94, while 24% of the cases had cells with 47 chromosomes of which the surplus chromosome corresponded to those of the group C and, in one case, of the group G. The occurence of cells with abnormal chromosome sets confirmed presence of clonal evolution. This was also a poor prognostic sign. By using cytogenetic of high accuracy and by studying further the chromosome abnormalities, problems concerning the importance of these abnormalities in the etiology and epidemiology of these diseases might be solved.

Chromosome Aberrations↗
PubMed2015

Clonality and intracellular polyploidy in virus evolution and pathogenesis.

In the present article we examine clonality in virus evolution. Most viruses retain an active recombination machinery as a potential means to initiate new levels of genetic exploration that go beyond those attainable solely by point mutations. However, despite abundant recombination that may be linked to molecular events essential for genome replication, herein we provide evidence that generation of recombinants with altered biological properties is not essential for the completion of the replication cycles of viruses, and that viral lineages (near-clades) can be defined. We distinguish mechanistically active but inconsequential recombination from evolutionarily relevant recombination, illustrated by episodes in the field and during experimental evolution. In the field, recombination has been at the origin of new viral pathogens, and has conferred fitness advantages to some viruses once the parental viruses have attained a sufficient degree of diversification by point mutations. In the laboratory, recombination mediated a salient genome segmentation of foot-and-mouth disease virus, an important animal pathogen whose genome in nature has always been characterized as unsegmented. We propose a model of continuous mutation and recombination, with punctuated, biologically relevant recombination events for the survival of viruses, both as disease agents and as promoters of cellular evolution. Thus, clonality is the standard evolutionary mode for viruses because recombination is largely inconsequential, since the decisive events for virus replication and survival are not dependent on the exchange of genetic material and formation of recombinant (mosaic) genomes.

Animals↗
PubMed2026

Paired Whole-Genome Sequencing of Scalp Angiosarcoma and Matched Lung Metastasis Reveals Common Clonal Origin and Lung-Specific Evolution.

Background and Clinical Significance: Cutaneous angiosarcoma frequently metastasizes to the lungs, where it may rarely present as diffuse cystic lung disease with recurrent pneumothorax, resulting in substantial diagnostic difficulty. We report a case of pulmonary metastatic cutaneous angiosarcoma in which paired whole-genome sequencing (WGS) of the primary and metastatic lesions was performed to clarify clonal origin and characterize metastatic evolution. Case Presentation: A 65-year-old man with recurrent right-sided pneumothorax and progressive bilateral cystic lung lesions underwent skin and lung biopsies. Histopathological examination and immunohistochemistry established the diagnosis of cutaneous angiosarcoma with pulmonary metastases. Paired WGS was performed on matched scalp and lung tumor specimens to evaluate shared and lesion-specific genomic alterations, pathway enrichment, and copy-number changes. Histopathology confirmed metastatic angiosarcoma involving the lungs. WGS identified 128 shared somatic alterations, supporting a common clonal origin, together with lung-specific and skin-specific mutations indicative of continued genomic divergence. Recurrent alterations involving POT1 and FLT4 were preserved in both lesions, whereas additional POT1 and TP53 alterations were detected only in the pulmonary metastasis. Pathway analysis demonstrated preferential enrichment of IGF1-mTOR, RAS, and WNT/LRP6 signaling in the metastatic lesion, while Gene Ontology analysis suggested functional divergence associated with metastatic progression. Conclusions: Pulmonary metastatic angiosarcoma should be considered in patients presenting with unexplained diffuse cystic lung disease and recurrent pneumothorax, particularly when pathological findings are inconclusive. Paired WGS complemented conventional histopathology by confirming the metastatic origin and providing insights into clonal evolution and lesion-specific molecular alterations, highlighting its potential value in the investigation of rare metastatic malignancies.

angiosarcoma↗
PubMed2026

Genomic characterization of aggressiveness in pituitary neuroendocrine tumors.

BACKGROUND: Aggressive evolution of PitNETs is rare; metastatic spread is even more. Defining aggressiveness and malignancy is challenging, subsequently hard to predict, and to understand. The aim was to provide a molecular definition of aggressiveness using genomic approaches. METHODS: PitNETs from 206 patients were included. Associations between 9 clinicopathological features of aggressiveness and PitNETs' omics were explored. Omics included transcriptome, DNA methylation, chromosomal alterations, and mutations. Clonal tumor evolution was monitored in 7 patients. RESULTS: Among the 9 clinicopathological features of aggressiveness, only rapid progression, progression after radiotherapy, Ki67/MIB1 proliferation index ≥10%, temozolomide treatment, metastases, and specific death were associated with specific omics signatures, while tumour maximal diameter ≥40 mm, cavernous, and sphenoid invasion were not. The omic signatures associated with these features of aggressiveness overlapped but remained distinct between corticotroph and mammo-somato-thyrotroph lineages. For each lineage, a common signature of aggressiveness was identified, associating a proliferative transcriptome signature and DNA hypermethylation. Alterations in specific genes were associated with aggressive features, including a novel PitNET gene, LRP1B, and known cancer genes (TP53, CDKN2A), while USP8 and GNAS alterations were not. Integration of gene alterations with methylome and transcriptome signatures isolated a subset of molecularly aggressive PitNETs. Molecular signatures were stable during the course of the disease, despite evolution toward aggressiveness and potential clonal divergence. CONCLUSION: This systematic analysis of clinicopathological features of aggressiveness using an integrated multiomic approach establishes a histomolecular definition of aggressiveness in PitNETs. Prospective cohort studies are needed to validate these molecular signatures and establish their prognostic value.

Humans↗
PubMed2026

Translational case series comparing next-generation sequencing profiles of primary breast cancer and brain metastases.

BACKGROUND: Breast cancer (BC) is a heterogeneous disease, and its molecular and immunohistochemical (IHC) profiles may change over time, particularly under therapeutic pressure. IHC discordance between primary tumors and BC brain metastases (BCBM) has been reported, yet its biological and clinical significance remains incompletely defined. Genomic profiling using next-generation sequencing (NGS) may provide additional insight into tumor evolution and clonal selection, although data from paired BC and BCBM are limited. METHODS: This translational case series included six patients randomly selected from an institutional cohort of BC patients who underwent neurosurgical resection of BCBM. IHC reassessment (ER, PR, and HER2) and NGS profiling using targeted panels were performed. RESULTS: Three of the six cases presented with IHC discordance, mainly loss of HR expression and gain of HER2 in BCBM. Genomic profiling identified 23 mutations in primary tumors compared with four in BCBM. BRCA1/2 variants predominated in primary tumors (21/23, 91%), most predicted to result in loss-of-function alterations. One mutation (PIK3CA/N345K) was shared between primary and metastatic tissues within the same patient. Overall survival ranged from 28 to 146 months. CONCLUSION: This paired analysis demonstrates immunophenotypic and genomic divergence between BC and BCBM, supporting the concept of dynamic tumor evolution. Receptor conversion and emergence or loss of actionable genomic alterations highlight the potential value of repeat molecular assessment in advanced stages. Although limited by a small sample size, retrospective design, and absence of matched germline testing, these findings reinforce the importance of integrating biomarker reevaluation into the management of selected patients.

Humans↗
PubMed2025

Unusual relapse dynamics in EGFR-mutated lung adenocarcinoma uncovered by genomic profiling: Insights from a case report.

Synchronous or metachronous multiple NSCLCs challenge clinical practice, particularly in distinguishing multiple separate primary lung cancers (SPLC) from intrapulmonary metastasis (IPM) for accurate staging and management. Here, we present a unique case of three resected lung adenocarcinomas (LUAD) from a single patient collected at different time points, all harboring the same EGFR p.L858R somatic driver mutation but exhibiting distinct clonal trajectories. Whole exome sequencing (WES) analysis revealed that the first tumor was an independent primary tumor, while the latter two tumors were clonally related. Our findings highlight the complexity of tumor progression and provide insights into clonal heterogeneity. This report underscores the importance of genomic profiling for discriminating SPLC from IPM and emphasizes that the detection of a single shared driver mutation is not sufficient to prove metastasis.

Humans↗
PubMed2026

Evolutionary and resistance dynamics in oligometastatic and oligoprogressive cancer treated with stereotactic radiotherapy and systemic therapies: A systematic review and focused meta-analysis.

BACKGROUND: Oligometastatic and oligoprogressive disease treated with stereotactic ablative radiotherapy (SABR) represents a clinically heterogeneous entity. Increasing evidence suggests that anatomical definitions alone may not adequately capture underlying biological diversity. This systematic review aimed to synthesize translational evidence exploring evolutionary dynamics, resistance mechanisms, and biomarker-driven stratification in patients treated with SABR. METHODS: A systematic literature review was performed including prospective and retrospective studies evaluating translational biomarkers in oligometastatic or oligoprogressive settings treated with SABR. Studies assessing genomic, transcriptomic, circulating or immune-related biomarkers were included. Data were summarized qualitatively according to predefined translational domains: (i) evolutionary dynamics under systemic therapy pressure, (ii) baseline biological stratification, (iii) longitudinal circulating biomarkers, and (iv) systemic immune remodeling. Exploratory quantitative visual syntheses were performed using reported hazard ratios when conceptually comparable endpoints were available. RESULTS: 19 studies comprising 1527 patients were included. Across tumor types and treatment contexts, translational analyses consistently indicated that anatomically defined oligometastatic states encompass biologically distinct subgroups with different risks of systemic progression. Studies evaluating oligoprogression under ongoing systemic therapy suggested a distinction between spatially constrained resistance and systemic molecular escape, supported by circulating tumor DNA and tissue- or plasma-based molecular profiling (including genomic and transcriptomic analyses). Baseline biological features, including adverse genomic signatures and circulating biomarkers, were associated with inferior progression outcomes despite metastasis-directed therapy. Longitudinal biomarkers provided early signals of treatment response and systemic control. Immune remodeling after SABR showed context-dependent effects, both systemic immune activation and treatment-related immunosuppression reported across studies.

Humans↗
PubMed2025

Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia.

Isocitrate dehydrogenase 1/2 (IDH) mutations are early initiating events in acute myeloid leukemia (AML). The complex clonal architecture and cellular heterogeneity in IDH-mutant AML underlies the heterogeneous clinical presentation and outcomes. Integrating single-cell genotyping and transcriptomics, we demonstrate a stem-like and inflammatory phenotype of IDH-mutant AML and identify clone-specific programs associated with NPM1, NRAS, and SRSF2 co-mutations. Furthermore, these clones had distinct responses to treatment with combination IDH inhibitors and chemotherapy, including elimination, reconstitution of myeloid differentiation, or retention within progenitor populations. At relapse after IDH inhibitor monotherapy, we identify upregulated stemness, inflammation, mitochondrial metabolism, and anti-apoptotic factors, as well as downregulated major histocompatibility complex (MHC) class II antigen presentation. At the pre-leukemic stage, we observe upregulation of IDH2-associated pathways, including inflammation. We deliver a detailed phenotyping of IDH-mutant AML and a framework for dissecting contributions of recurrently mutated genes in AML at diagnosis and following therapy, with implications for precision medicine.

Leukemia, Myeloid, Acute↗
PubMed1975

Chromosome aberrations in Syrian hamster embryo cells transformed after exposure to ultraviolet-irradiated herpes simplex virus type 1 or 2.

Six Syrian hamster embryo cell lines (14-012-8-1, KOS-6-1, 333-8-9, 333-2-29, MS-4-1, FR-6-1), developed after exposure of primary cultures to different strains of UV-irradiated herpes simplex virus (HSV) type 1 or 2, were analyzed for chromosome aberrations. All the cell lines showed chromosome stability (number of chromosomes were maintained within a narrow range of variation in the diploid region) and a low incidence of polyploids, endoreduplications, and metaphases with pulveration or extensively fragmented chromosomes. The cell lines, passaged over long periods of time in vitro, developed marker chromosomes that suggested a clonal-type evolution of the cell populations. Two cell lines, 333-8-9 and 14-012-8-1, showed two different marker chromosomes with large heterochromatic regions. Chromosomes with abnormal heterochromatic regions, which often appeared like prominent secondary constrictions, were found in all the cell lines we examined. The level of chromosome breakage was low in all the cell lines except the highly tumorigenic cell line 333-2-29, which had a high incidence of cells with single or double chromatinic bodies. The abnormal heterochromatic regions that occurred on marker chromosomes and prominent secondary constrictions were interpreted as a possible chromosomal effect of the HSV. The karyotypic stability and low incidence of open breaks might have been the result of UV irradiation of the HSV.

Animals↗
PubMed2026

NTRK-positive collision tumor of the gastrointestinal tract: a rare entity case report.

Neurotrophic receptor tyrosine kinase (NTRK) fusion-positive colorectal cancer (CRC) represents a rare molecular subset of CRC. We report an exceptional case of a collision tumor composed of two anatomically adjacent but histologically and genomically distinct primary colorectal carcinomas, each giving rise to a corresponding metastasis. Comprehensive histopathologic and molecular analyses demonstrated that one primary tumor and its matched metastasis consisted predominantly (> 90%) of a solid carcinoma harboring a TPR::NTRK fusion, high microsatellite instability (MSI-H), elevated tumor mutational burden (TMB), and loss of MLH1 and PMS2 expression by immunohistochemistry. In contrast, the second primary tumor and its corresponding metastasis exhibited conventional adenocarcinoma morphology with mucinous differentiation, lacked an NTRK fusion, and carried canonical driver mutations in KRAS, APC, SMAD4, and TP53. This case underscores the importance of integrated histopathologic and molecular evaluation in CRCs with heterogeneous morphology, as the identification of multiple, genomically distinct tumor components may have significant diagnostic, prognostic, and therapeutic implications.

NTRK gene fusion↗