Genetic Counseling in Renal Masses

All urologists have faced patients suffering a renal cancer asking for the occurrence of the disease in their offspring and very often the answer to this question has not been well founded from the scientific point of view, and only in few cases a familial segregation tree is performed. The grate shift seen in the detection of small renal masses and renal cancer in the last decades will prompt us to know the indications for familial studies, which and when are necessary, and probably to refer those patients with a suspected familial syndrome to specialized oncological centers where the appropriate molecular and familial studies could be done. Use of molecular genetic testing for early identification of at-risk family members improves diagnostic certainty and would reduce costly screening procedures in at-risk members who have not inherited disease-causing mutations. This review will focus on the molecular bases of familial syndromes associated with small renal masses and the indications of familial studies in at-risk family members

Cytochrome P17 inhibition with ketoconazole as treatment for advanced granulosa cell ovarian tumor

Originally published by the American Society of Clinical Oncology. García-Donas et al.: Journal of Clinical Oncology Vol. 31.10, April 1 - 2013: e165-e16

Suitability of melanoma FFPE samples for NGS libraries: time and quality thresholds for downstream molecular tests

The use of NGS in clinical practice for precision diagnosis requires a quality starting material. Despite the broadly established use of formalin-fixed paraffin-embedded (FFPE) samples in molecular testing, these usually have low-quality DNA. We established a method to determine the suitability of melanoma FFPE samples for an amplicon-based NGS custom panel analysis. DNA was extracted from unstained melanoma samples and wide local excision samples. Amplicon-based libraries were constructed and tested using time and quality parameters as variables. Time elapsed from sample retrieval >7 years, a quality control value > 5.63 and a DNA integrity value < 2.05 indicated samples were not suitable. A decision tree is provided with rate of samples suitable for analysis according to the combination of these parametersThis study has been funded by the Instituto de Salud Carlos III grant number PI15/01860, the Junta Provincial de Valencia de la Asociación Española contra el Cancer through a PhD grant, and by the Universidad Católica de Valencia San Vicente Mártir. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscrip

Molecular characterization and clinical impact of TMPRSS2-ERG rearrangement on prostate cancer: comparison between FISH and RT-PCR

Prostate cancer (PCa) is a very heterogeneous disease, and there are constraints in its current diagnosis. Serum PSA levels, digital rectal examination (DRE), and histopathologic analysis often drive to overdiagnosis and overtreatment. Since 2005, the presence of the genetic rearrangement between transmembrane-serine protease gene (TMPRSS2) and the erythroblast transformation-specific (ETS)member ERG (v-ets erythroblastosis virus E26 oncogene homolog avian) has been demonstrated in almost half of PCa cases. Both FISH and RT-PCR are useful tools for detecting these rearrangements, but very few comparatives between both techniques have been published. In this study, we included FFPE tumors from 294 PCa patients treated with radical prostatectomy with more than 5 years of followup.We constructed a total of 20 tissue microarrays in order to perform break-apart and tricolor probe FISH approaches that were compared with RT-PCR, showing a concordance of 80.6% ( P < 0.001). The presence of TMPRSS2-ERG rearrangement was observed in 56.6% of cases. No association between TMPRSS2-ERG status and clinicopathological parameters nor biochemical progression and clinical progression free survival was found. In conclusion, this study demonstrates that both FISH and RT-PCR are useful tools in the assessment of the TMPRSS2-ERG fusion gene status in PCa patients and that this genetic feature per se lacks prognostic value.This study has been funded by the Grants FIS PI06/01619 and PI10/01206 from the Instituto de Salud Carlos III, Madrid, ACOMP 12/029 from the Generalitat Valenciana, Valencia, and Astra Zeneca, Spain

Mutational Characterization of Cutaneous Melanoma Supports Divergent Pathways Model for Melanoma Development

This article belongs to the Special Issue Melanoma: Prevention and Molecular Epidemiology.[Simple Summary] The divergent pathway model established at least two approaches for melanoma development. One was related to a propensity to melanocytic proliferation (nevogenic), and the other was associated with an accumulation of solar damage (CSD). We conducted a retrospective study to examine whether this model had a molecular support using sequencing and bioinformatic tools on a set of cutaneous melanomas corresponding to these two groups. We found that the nevogenic melanomas were associated with mutations in BRAF, while the CSD melanomas were associated with mutations in NF1, ROS1, GNA11, and RAC1. We concluded that nevogenic and CSD melanomas constitute two different biological entities.[Abstract] According to the divergent pathway model, cutaneous melanoma comprises a nevogenic group with a propensity to melanocyte proliferation and another one associated with cumulative solar damage (CSD). While characterized clinically and epidemiologically, the differences in the molecular profiles between the groups have remained primarily uninvestigated. This study has used a custom gene panel and bioinformatics tools to investigate the potential molecular differences in a thoroughly characterized cohort of 119 melanoma patients belonging to nevogenic and CSD groups. We found that the nevogenic melanomas had a restricted set of mutations, with the prominently mutated gene being BRAF. The CSD melanomas, in contrast, showed mutations in a diverse group of genes that included NF1, ROS1, GNA11, and RAC1. We thus provide evidence that nevogenic and CSD melanomas constitute different biological entities and highlight the need to explore new targeted therapies.This study was supported by the Ministerio de Ciencia e Innovación-Instituto de Salud Carlos III (PI15/01860; PI19/00667), the Asociación Española Contra el Cáncer-Valencia through “Ayudas predoctorales en Oncología” grant, and the European Academy of Dermatology and Venereology (PPRC-2018-36)

Mutational Characterization of Cutaneous Melanoma Supports Divergent Pathways Model for Melanoma Development

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-14, pub-electronic 2021-10-18Publication status: PublishedFunder: Instituto de Salud Carlos III; Grant(s): PI15/01860; PI19/00667Funder: EADV; Grant(s): PPRC-2018-36, Ayuda predoctoral en OncologíaAccording to the divergent pathway model, cutaneous melanoma comprises a nevogenic group with a propensity to melanocyte proliferation and another one associated with cumulative solar damage (CSD). While characterized clinically and epidemiologically, the differences in the molecular profiles between the groups have remained primarily uninvestigated. This study has used a custom gene panel and bioinformatics tools to investigate the potential molecular differences in a thoroughly characterized cohort of 119 melanoma patients belonging to nevogenic and CSD groups. We found that the nevogenic melanomas had a restricted set of mutations, with the prominently mutated gene being BRAF. The CSD melanomas, in contrast, showed mutations in a diverse group of genes that included NF1, ROS1, GNA11, and RAC1. We thus provide evidence that nevogenic and CSD melanomas constitute different biological entities and highlight the need to explore new targeted therapies

KIT mutational status does not constitute an independent prognostic marker in cutaneous melanoma. A study on 688 Spanish patients

In this study, we aimed to determine the prognostic potential of KIT+ in cutaneous melanoma. We selected a large cohort of 686 stage I-III Spanish cutaneous melanoma patients treated at the Fundación Instituto Valenciano de Oncología (FIVO) between 2000 and 2020Medicin

Germline cancer-related mutations detected by routine targeted NGS for tumour analysis: A series of 357 melanoma patients

Screening for somatic mutations using next-generation sequencing (NGS) is the standard of care for many cancers to select the most appropriate tratment. Ideally, matched tumour-normal (T/N) sequencing allows the identification of true somatic mutations. This approach may also identify incidental germline pathogenic variants associated with inherited syndromesThis study was supported in part by Project PROMETEO21/067, Generalitat ValencianaMedicin

Expression profiles of angiogenesis in two high grade chondrosarcomas: A xenotransplant experience in nude mice

Background. Chondrosarcomas (Chs) are malignant cartilage-forming tumors that represent the third most common malignant solid tumor of bone in adults. Angiogenesis is a major factor for tumor growth and metastasis. Our aim was to make a histological, immunohistochemical, ultrastructural and molecular characterization of the neovascularization established between xenotransplanted Chs and the host during the initial phases of growth in nude transfer, in order to find potential markers for distinguishing between high grades II and III Chs. Methods. two xenotransplanted high grade human Chs were evaluated. Tumor pieces were implanted subcutaneously on the backs of 14 athymic Balb-c nude mice. The animals were sacrificed 24, 48, and 96 hours; and 7, 14, 21 and 28 days after implantation. Two grade I Chs were also transferred in nude but did not grow. Results. Morphological differences were apparent between these two Chs during the early stages of neoplastic growth. Immunohistochemistry demonstrated overexpression of pro-angiogenic factors 24h-48h after tumor implantation. Additionally, neoplastic cells co-expressed chemokines (CXCL9, CXCL10 and GRO) and their receptors. Molecular studies showed two expression profiles, revealing an early and a late phase in the angiogenic process. Conclusion. High grade Chs demonstrated two different stages of induced angiogenesis, with an intimate association between structural and molecular events that might explain the different aggressive biological behavior of grade II and III Chs. The present model may be useful for testing the effect of anti-angiogenic drugs