Genes, Chromosomes & Cancer最新文献

Recurrent KMT2A and YAP1 related fusions have recently been reported in various mesenchymal neoplasms of different histogenesis. First, YAP1::KMT2A fusions have been described in a subset of MUC4-negative sclerosing epithelioid fibrosarcomas (SEF), while VIM::KMT2A fusions in a handful of cases associated with an undifferentiated spindle cell phenotype lacking stromal hyalinization. On the other hand, YAP1 gene rearrangements have been reported in a wide spectrum of sarcomas, including vascular neoplasms such as epithelioid hemangioendothelioma (EHE). Despite these molecular advances, occasional challenges in classification may occur even if the pathognomonic fusion is identified. In this study, we report such a case of a soft tissue sarcoma displaying an unusual morphology and immunoprofile, which remained unclassified even after a YAP1::KMT2A fusion was detected. The lesion occurred in the left leg of a 65-year-old female and microscopically closely resembled a SEF, with epithelioid morphology organized in cords, nests, and sheets in a heavy hyalinized background. Focally, the cells showed cytoplasmic vacuoles with eosinophilic material, reminiscent of the “blisters cells” seen in EHE. Moreover, by immunohistochemistry (IHC), the tumor showed diffuse reactivity for vascular markers, including ERG, CD31, CD34, and D2-40, as well as for TFE3, while being negative for MUC4, CAMTA1, smooth-muscle actin, desmin, S100 and keratins. Targeted RNA sequencing revealed a YAP1::KMT2A fusion. Based on this molecular result and the conflicting morphologic and IHC findings, a definitive distinction between a MUC4-negative SEF and an EHE could not been established. To further subclassify the lesion, subsequent clustering analysis using RNAseq signature was performed against a vast group of sarcoma types on the same array. Results showed that the tumor was in close proximity to the SEF group, admixed together with the other YAP1::KMT2A MUC4 negative SEF sarcomas. This case is highly instructive, as it shows another application of RNA sequencing in clinical practice when discordant or uncertain results between pathologic findings and fusion type may occur. Indeed, RNAseq signature could help, in this context, to better classify the tumor as a YAP1::KMT2A sarcoma instead of a vascular tumor. Larger series are needed to evaluate the pathogenesis of these tumors and the relevance of vascular markers expression.

J. Vega-Gonzalez, J. A. C. Toro, E. L. García, G. Marquina, M. d. l. T. Serrano, A. M. C. Gallardo, R. B. Giménez, D. H. Martínez, A. G. Egido, L. A. García, L. Nielsen, J. C. Plaza, and L. O. Medina, “EWSR1::SSX1 Fusion-Driven Synovial Sarcoma: A Case Presentation and Review of the Literature,” Genes Chromosomes Cancer 64 (2025): e70048, https://doi.org/10.1002/gcc.70048.

This article was originally published with the incorrect article category of “Review Article.” The correct category is Brief Report. This has been corrected in the online version of the article.

We apologize for this error.

The molecular characteristics of switch/sucrose non-fermentable-related BAF chromatin remodeling complex subunit B1 (SMARCB1)-deficient renal cell carcinoma (RCC), particularly in patients without any hemoglobinopathies, remain unknown. Furthermore, the molecular similarities between SMARCB1-deficient RCC without hemoglobinopathies and renal medullary carcinoma (RMC), as well as malignant rhabdoid tumor of the kidney (MRTK), have not been clarified. In this study, we analyzed the mRNA and protein expressions of three SMARCB1-deficient RCCs without hemoglobinopathies using the nCounter Gene Expression Assay, immunohistochemistry (IHC), and quantitative real-time polymerase chain reaction (qPCR), and compared them with those of MRTKs. As results from nCounter, the mRNA expression patterns of SMARCB1-deficient RCC and MRTK differed completely from each other. We identified 93 genes, including BCL2, that were significantly upregulated in SMARCB1-deficient RCC. Enrichment analysis revealed that PI3K Akt signaling was an enriched term in SMARCB1-deficient RCC but not in MRTK. The immunohistochemical expressions of Bcl-2 in SMARCB1-deficient RCC and MRTK supported the nCounter results. Our data showed that SMARCB1-deficient RCC without hemoglobinopathies is a distinct entity from MRTK. We also discussed possible clinicopathological and molecular differences between SMARCB1-deficient RCC without hemoglobinopathies and RMC. The distinctions among these SMARCB1-deficient renal tumors identified in our study would significantly enhance diagnosis and develop new therapeutic strategies.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare and clinically aggressive variant of inflammatory myofibroblastic tumor (IMT). It typically presents in children and young adults, often affecting the abdominal cavity. It is characterized by the presence of plump, polyhedral, and epithelioid cells, and a distinctive nuclear or perinuclear ALK staining on immunohistochemistry. Various ALK fusion partners have been identified in EIMS, including RANBP2, RRBP1, EML4, and VCL. In this report, we present four cases of EIMS involving the abdominal cavity, including the first case with a CLTC::ALK fusion, which has previously been associated only with nonaggressive IMT.

Chromosomal translocations are key events in cancer, driving oncogenesis by disrupting and deregulating critical genes. While specific tumor-associated translocations are well studied, the frequencies and distributions of most remain unknown. Additionally, the role of chromosomal reshuffling in translocations has received little attention. This study presents data on the chromosomal involvement in 59 251 translocations reported in 58 tumor entities, including both benign and malignant tumors. Unlike studies focusing on tumor-specific abnormalities identified at the chromosome band level, this study examines translocations at the chromosomal level, offering a novel perspective on their distribution. This broader approach aims to uncover patterns that do not emerge or are disregarded in studies limited to tumor-specific aberrations. The resulting dataset provides a novel resource for deepening our understanding of the chromosomal origins of translocations in neoplasia. Comparisons of translocation frequency distributions among tumor types, when excluding the characteristic tumor-associated translocations, revealed that the patterns of chromosomal involvement in translocations are largely unique to each tumor entity. Statistical analyses of 241 pairwise comparisons of translocation spectra within hematologic disorders, solid tumors, and between groups of hematologic malignancies and both benign and malignant solid tumors showed insignificant/very weak associations (R² ≤ 0.3) in 98% of the comparisons. The findings hence demonstrate that different tumor types are characterized by distinct chromosomal translocation signatures, strongly suggesting that most translocations encountered in tumor cells are not merely random events. Consequently, our study highlights the potential of rare translocations to serve as indicators of disease-specific processes.

Pediatric fibroblastic, myofibroblastic, and myoid tumors encompass several entities, many with characteristic gene fusions that are now emerging as molecularly defined tumor groups. Here, we present two cases of spindle cell neoplasms with novel ACTB::FER promoter swap fusions. Both tumors presented in the extremities of pediatric patients (9-year-old and 6-year-old females) as superficial skin nodules with slow growth. Histologically, both tumors showed monomorphic spindle cell proliferation in short fascicles, but without significantly increased mitotic activity, high-grade atypia, or necrosis. Both cases showed diffuse positivity for SMA with patchy desmin expression. RNA sequencing confirmed fusion breakpoints, revealing transcriptional upregulation of FER. Neither patient has had evidence of interval growth or recurrence to date. While the biological significance of ACTB::FER fusions remains unclear, their recurrence and the absence of other clear oncogenic drivers suggest a distinct molecular pathway that may define a novel entity. Fusions of ACTB and FER genes with different partners have been observed in rare aggressive mesenchymal tumors; however, the ACTB::FER promoter swap fusion is currently unrecognized in soft tissue tumors. We report the first two cases of soft tissue tumors harboring ACTB::FER fusions and expand the molecular spectrum of mesenchymal tumors with kinase gene alterations. Further, we highlight the importance of target-agnostic approaches for the detection of rare kinase fusions, which may not be included on targeted next-generation sequencing panels.