0000000000004528
AUTHOR
Susana Martín-vañó
showing 8 related works from this author
Congenital undifferentiated sarcoma associated to BCOR-CCNB3 gene fusion
2017
Small round cell sarcomas are aggressive bone and soft tissue tumors that predominantly affect children and young adults. A new group of sarcomas with a recurrent BCOR-CCNB3 gene fusion has been recently identified in previously unclassifiable small round cell sarcomas. BCOR-CCNB3 sarcomas share clinical and pathologic similarities with Ewing sarcoma, but show a stronger male predilection and less aggressiveness, as well as distinct gene expression profiling and pangenomic SNP array analyses. We report the unusual case of a congenital BCOR-CCNB3 retroperitoneal sarcoma in a female born at 34th gestational week, which was diagnosed in necropsy after 21hours of life. Immunohistochemical analy…
Intra-Tumour Genetic Heterogeneity and Prognosis in High-Risk Neuroblastoma
2021
Simple Summary Neuroblastoma (NB) is the most common extra-cranial solid paediatric cancer and is responsible for 15% of childhood cancer deaths. Patients with NB are characterized by presenting a very heterogeneous clinic (inter-tumoural heterogeneity) and also both spatial and temporal intra-tumour heterogeneity (ITH) reflected in their genetic aberrations, which may be the consequence of the coexistence of different microenvironments within the tumour. Applying pangenomic techniques to detect genomic aberrations in different biopsies (solid and liquid) of high risk NB (HR-NB) we have detected spatial ITH in a surprisingly high percentage (almost 40%) of the studied cohort. Moreover, a po…
Unraveling the extracellular matrix-tumor cell interactions to aid better targeted therapies for neuroblastoma
2021
Treatment in children with high-risk neuroblastoma remains largely unsuccessful due to the development of metastases and drug resistance. The biological complexity of these tumors and their microenvironment represent one of the many challenges to face. Matrix glycoproteins such as vitronectin act as bridge elements between extracellular matrix and tumor cells and can promote tumor cell spreading. In this study, we established through a clinical cohort and preclinical models that the interaction of vitronectin and its ligands, such as αv integrins, are related to the stiffness of the extracellular matrix in high-risk neuroblastoma. These marked alterations found in the matrix led us to speci…
Tumor de Wilms: estudio morfológico, inmunohistoquímico y genético de un caso de nefroblastoma con diferenciación rabdomioblástica
2016
Resumen El tumor de Wilms es el tumor renal primario mas frecuente en la infancia, y afecta a uno de cada 10.000 ninos en Estados Unidos. Tipicamente se muestra como un tumor trifasico con componente epitelial, blastemal y estromal, pudiendo presentar areas de anaplasia y diferenciaciones hacia otros tejidos. En cuanto a su genetica, se han descrito varios genes relacionados en su desarrollo. En el presente trabajo se realizo un estudio anatomopatologico, ademas de uno pangenomico mediante el chip de single nucleotide polymorphism (SNP) HumanCytoSNP-12. En el caso que se presenta se observo un tumor trifasico con diferenciacion rabdomioblastica solo visible mediante tinciones inmunohistoqui…
Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14)
2021
Abdominal aortic aneurysm (AAA), is a complex disorder characterized by vascular vessel wall remodeling. LIGHT (TNFSF14) is a proinflammatory cytokine associated with vascular disease. In the present study, the impact of genetic inactivation of Light was investigated in dissecting AAA induced by angiotensin II (AngII) in the Apolipoprotein E-deficient (Apoe−/−) mice. Studies in aortic human (ah) vascular smooth muscle cells (VSMC) to study potential translation to human pathology were also performed. AngII-treated Apoe−/−Light−/− mice displayed increased abdominal aorta maximum diameter and AAA severity compared with Apoe−/− mice. Notably, reduced smooth muscle α-actin+ area and Acta2 and C…
Female New-Born with Undifferentiated Sarcoma Defined by Bcor-Ccnb3 Fusion Transcript
2015
A female new-born presented with a sacrococcygeal mass with spinal cord compression. A preliminary histologic diagnosis determined a small round blue cell tumor and immunohistochemical results discarded neuroblastoma, rhabdomyosarcoma, rhabdoid tumor, Ewing or peripheral neuroectodermal tumor (PNET). The results obtained by SNPa showed a chromosome Xp11.4 deletion of 0.9 Mb, where the BCOR gene is located. RT-PCR did not detect the ETV6-NTRK3 or EWSR1-FLI1 fusion, but did reveal the presence of the BCOR-CCNB3 fusion transcript, recently reported in some undifferentiated sarcomas, establishing the diagnosis of “Ewing-like” sarcoma. Analysis of CCNB3 expression by immunohistochemistry showed …
Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes
2021
Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor SNP array profiles from 127 HR-NB patients: (1) Copy number aberration burden (%gainslength+%losseslength), (2) copy number load (CNL) (%gainslength-%losseslength) and (3) net genomic load (NGL) (%gainsamount-%lossesamount). Tumors were classified according to positive or negative CNL and NGL genomic subtypes. The impact of the genomic instability indexes on overall survival (OS) was assessed with…
Digital Image Analysis Applied to Tumor Cell Proliferation, Aggressiveness, and Migration-Related Protein Synthesis in Neuroblastoma 3D Models
2020
Patient-derived cancer 3D models are a promising tool that will revolutionize personalized cancer therapy but that require previous knowledge of optimal cell growth conditions and the most advantageous parameters to evaluate biomimetic relevance and monitor therapy efficacy. This study aims to establish general guidelines on 3D model characterization phenomena, focusing on neuroblastoma. We generated gelatin-based scaffolds with different stiffness and performed SK-N-BE(2) and SH-SY5Y aggressive neuroblastoma cell cultures, also performing co-cultures with mouse stromal Schwann cell line (SW10). Model characterization by digital image analysis at different time points revealed that cell pro…