scholarly journals Case Report: Differential Genomics and Evolution of a Meningeal Melanoma Treated With Ipilimumab and Nivolumab

2022 ◽  
Vol 11 ◽  
Author(s):  
Remberto Burgos ◽  
Andrés F. Cardona ◽  
Nicolas Santoyo ◽  
Alejandro Ruiz-Patiño ◽  
Juanita Cure-Casilimas ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Genetic Alterations ◽  
Interesting Case ◽  
Biological Behavior ◽  
High Recurrence Rate ◽  
Review Of The Literature ◽  
Rna Translation ◽  
Melanocytic Tumors ◽  
Clonal Origin ◽  
Multiple Therapy

Primary melanocytic tumors of the CNS are extremely rare conditions, encompassing different disease processes including meningeal melanoma and meningeal melanocytosis. Its incidence range between 3-5%, with approximately 0.005 cases per 100,000 people. Tumor biological behavior is commonly aggressive, with poor prognosis and very low survivability, and a high recurrence rate, even after disease remission with multimodal treatments. Specific genetic alterations involving gene transcription, alternative splicing, RNA translation, and cell proliferation are usually seen, affecting genes like BRAF, TERT, GNAQ, SF3B1, and EIF1AX. Here we present an interesting case of a 59-year-old male presenting with neurologic symptoms and a further confirmed diagnosis of primary meningeal melanoma. Multiple therapy lines were used, including radiosurgery, immunotherapy, and chemotherapy. The patient developed two relapses and an evolving genetic makeup that confirmed the disease’s clonal origin. We also provide a review of the literature on the genetic basis of primary melanocytic tumors of the CNS.

Genetic Alterations at 13q14 May Correlate with Differences in the Biological Behavior of Prostate Cancer between Japanese and Caucasian Men

2010 ◽  
Vol 84 (4) ◽  
pp. 461-466 ◽  
Author(s):  
Taku Misumi ◽  
Yoshiaki Yamamoto ◽  
Tomoyuki Murakami ◽  
Yoshihisa Kawai ◽  
Hideaki Ito ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Alterations ◽  
Biological Behavior ◽  
Caucasian Men

scholarly journals Mitochondrial Syndromes Revisited

2021 ◽  
Vol 10 (6) ◽  
pp. 1249
Author(s):  
Daniele Orsucci ◽  
Elena Caldarazzo Ienco ◽  
Andrea Rossi ◽  
Gabriele Siciliano ◽  
Michelangelo Mancuso
Keyword(s):  
Clinical Trials ◽  
Genetic Basis ◽  
Phenotypic Variability ◽  
Mitochondrial Diseases ◽  
Genetic Alterations ◽  
Mitochondrial Disorders ◽  
Single Mutation ◽  
Multicenter Studies ◽  
Future Studies ◽  
Clinical Syndromes

In the last ten years, the knowledge of the genetic basis of mitochondrial diseases has significantly advanced. However, the vast phenotypic variability linked to mitochondrial disorders and the peculiar characteristics of their genetics make mitochondrial disorders a complex group of disorders. Although specific genetic alterations have been associated with some syndromic presentations, the genotype–phenotype relationship in mitochondrial disorders is complex (a single mutation can cause several clinical syndromes, while different genetic alterations can cause similar phenotypes). This review will revisit the most common syndromic pictures of mitochondrial disorders, from a clinical rather than a molecular perspective. We believe that the new phenotype definitions implemented by recent large multicenter studies, and revised here, may contribute to a more homogeneous patient categorization, which will be useful in future studies on natural history and clinical trials.

Resolution of Optic Disc Pit Maculopathy Following Posterior Vitreous Detachment

2021 ◽  
pp. 247412642110467
Author(s):  
Ali H. Mannaa ◽  
Reda A. Issa ◽  
J. Shepard Bryan
Keyword(s):  
Optic Disc ◽  
Posterior Vitreous Detachment ◽  
Interesting Case ◽  
Optic Disc Pit ◽  
Review Of The Literature ◽  
Fluid Accumulation ◽  
Optic Pit ◽  
Vitreous Detachment ◽  
Spontaneous Improvement ◽  
Optic Disc Pit Maculopathy

Purpose: This work presents a case of significant improvement of optic pit disc maculopathy following an acute posterior vitreous detachment (PVD) and discusses the possible mechanisms of this phenomenon. Methods: A case report and review of the literature are presented. Results: A 56-year-old man presenting with progressive visual decline in his left eye was found to have an optic disc pit with optical coherence tomography (OCT) evidence of severe intraretinal edema and maculoschisis. His visual acuity and macular anatomy on OCT improved dramatically in the months following a PVD. Conclusions: This report presents an interesting case of spontaneous improvement of optic disc pit–related maculopathy following PVD. We discuss the cause of the retinal fluid accumulation in optic disc pit maculopathy and consider that the OCT findings in our case lend credence to the theory that this fluid originates from the vitreous humor.

scholarly journals Interesting Case of Skin Metastasis in Colorectal Cancer and Review of Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
J. M. V. Amarjothi ◽  
R. Villalan ◽  
J. Jeyasudhahar ◽  
O. L. NaganathBabu
Keyword(s):  
Colorectal Cancer ◽  
Curative Resection ◽  
Adverse Outcome ◽  
Molecular Profiling ◽  
Interesting Case ◽  
Skin Metastasis ◽  
Biological Behavior ◽  
Review Of Literature

Skin metastasis is a complication rarely seen after curative resection for colorectal cancer and chemotherapy. The article describes a metachronous case of skin metastasis after curative resection. This article is presented to illustrate that genetic and molecular profiling of carcinoma is a must for diagnosis of aggressive biological behavior and that skin metastasis is usually a harbinger of adverse outcome.

Primary Leptomeningeal Melanocytic Tumors of the Spine: Report of Two Cases and Review of the Literature

2019 ◽  
Vol 124 ◽  
pp. 228-236
Author(s):  
Frederik Kinnen ◽  
Steffen K. Fleck ◽  
Jörg Baldauf ◽  
Volkmar Hans ◽  
Georg Daeschlein ◽  
...  
Keyword(s):  
Review Of The Literature ◽  
Melanocytic Tumors

scholarly journals Highly Prevalent Genetic Alterations in Receptor Tyrosine Kinases and Phosphatidylinositol 3-Kinase/Akt and Mitogen-Activated Protein Kinase Pathways in Anaplastic and Follicular Thyroid Cancers

2008 ◽  
Vol 93 (8) ◽  
pp. 3106-3116 ◽  
Author(s):  
Zhi Liu ◽  
Peng Hou ◽  
Meiju Ji ◽  
Haixia Guan ◽  
Kimberly Studeman ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tyrosine Kinases ◽  
Genetic Basis ◽  
Receptor Tyrosine Kinases ◽  
Genetic Alterations ◽  
Akt Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Thyroid Cancers ◽  
Mapk Pathways ◽  
Phosphatidylinositol 3

Abstract Context: Genetic alterations in receptor tyrosine kinases (RTKs) and phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK pathways have not been fully defined in anaplastic and follicular thyroid cancers [anaplastic thyroid cancer (ATC), follicular thyroid cancer (FTC)]. Objective: The objective of the study was to explore a wide-range genetic basis for the involvement of these pathways in ATC. Design: We examined mutations and copy number gains of a large panel of genes in these pathways and corresponding phosphorylation of ERK (p-ERK) and Akt. Results: We found frequent copy gains of RTK genes, including EGFR, PDGFRα and -β, VEGFR1 and 2, KIT, and MET and in PIK3Ca, PIK3Cb, and PDK1 genes in the PI3K/Akt pathway. Mutations of Ras, PIK3Ca, PTEN, and BRAF genes and RET/PTC rearrangements were common, whereas mutations in PDK1, Akt1, Akt2, and RTK genes were uncommon in ATC. Overall, 46 of 48 ATC (95.8%) harbored at least one genetic alteration, and coexistence of two or more was seen in 37 of 48 ATC (77.1%). These genetic alterations were somewhat less common in FTC. Genetic alterations that could activate both the PI3K/Akt and MAPK pathways were found in 39 of 48 ATC (81.3%). RTK gene copy gains were preferentially associated with p-Akt, suggesting their dominant role in activating the PI3K/Akt pathway. The phosphorylation of Akt was far more common than p-ERK in FTC, and both were relatively common and often coexisted in ATC. Conclusions: Genetic alterations in the RTKs and PI3K/Akt and MAPK pathways are extremely prevalent in ATC and FTC, providing a strong genetic basis for an extensive role of these signaling pathways and the development of therapies targeting these pathways for ATC and FTC, particularly the former.

scholarly journals Ret/PTC activation does not influence clinical and pathological features of adult papillary thyroid carcinomas

2003 ◽  
pp. 505-513 ◽  
Author(s):  
E Puxeddu ◽  
S Moretti ◽  
A Giannico ◽  
M Martinelli ◽  
C Marino ◽  
...  
Keyword(s):  
Genetic Study ◽  
Genetic Alterations ◽  
Biological Behavior ◽  
Tyrosine Kinase Domain ◽  
Fisher Exact Test ◽  
Pathological Features ◽  
Papillary Thyroid ◽  
Association Analyses ◽  
Thyroid Carcinomas ◽  
Clinical And Pathological Features

OBJECTIVE: RET proto-oncogene rearrangements (ret/PTCs) represent the most common genetic alterations found in papillary thyroid carcinomas (PTCs). Correlation of ret/PTC expression with clinical outcome is controversial. The aim of the present study was to analyze the frequency of RET rearrangements in adult PTCs, and to investigate if ret/PTCs influence biological behavior and clinical features of the cancers. DESIGN: Ret/PTC rearrangements were looked for in tIssue samples of 48 PTCs collected at our institution. Data about clinical and pathological features of the tumors were also reviewed. Three separate association analyses were carried out on the cohort evaluating the effects of, respectively, ret/PTC positivity, preferential RET tyrosine kinase domain (RET-TK) expression, and ret/PTC plus RET-TK positivity, on age, sex, tumor size, staging, number of neoplastic foci, and histological subtype. METHODS: The genetic study was conducted with the RT-PCR-Southern blot technique. Standard Student's t-test and Fisher exact test were applied for the association analyses. RESULTS: The molecular genetic study demonstrated the positivity of ret/PTC1 and ret/PTC3 in 13 of 48 tumors (27.1%), and an exclusive or preferential RET-TK expression in 17 cases (35.4%). None of the three genetico-clinical analyses showed any significant association between ret/PTC expression and the clinical and pathological features of the cancers. CONCLUSIONS: These data indicate that RET rearrangements may not play any distinctive role in driving histotype development and cancer progression in these neoplasms. Moreover, they weaken the possibility of using ret/PTC as a prognostic marker for papillary thyroid carcinomas.

scholarly journals Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Xi Chen ◽  
Xiaohong Kong ◽  
Jie Zhu ◽  
Tingting Zhang ◽  
Yanwei Li ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Genetic Alterations ◽  
Chinese Patients ◽  
Study Cohort ◽  
Chinese Han ◽  
Hormone Synthesis ◽  
Functional Studies ◽  
Pathogenic Variants ◽  
Thyroid Dyshormonogenesis ◽  
Generation Sequencing

Objective. Thyroid dyshormonogenesis (DH) is a genetically heterogeneous inherited disorder caused by thyroid hormone synthesis abnormalities. This study aims at comprehensively characterizing the mutation spectrum in Chinese patients with DH. Subjects and Methods. We utilized next-generation sequencing to screen for mutations in seven DH-associated genes (TPO, DUOX2, TG, DUOXA2, SLC26A4, SLC5A5, and IYD) in 21 Chinese Han patients with DH from Xinjiang Province. Results. Twenty-eight rare nonpolymorphic variants were found in 19 patients (90.5%), including 19, 5, 3, and 1 variants in DUOX2, TG, DUOXA2, and SLC26A4, respectively. Thirteen (62%) patients carried monogenic mutations, and six (28.5%) carried oligogenic mutations. Fifteen (71%) patients carried 2 or more DUOX2 (14) or DUOXA2 (1) variants. The genetic basis of DH in nine (43%) patients harboring biallelic or triallelic pathogenic variants was resolved. Seventeen patients (81%) carried DUOX2 mutations, most commonly p.R1110Q or p.K530X. No correlations were found between DUOX2 mutation types or numbers and clinical phenotypes. Conclusions. DUOX2 mutations were the most predominant genetic alterations of DH in the study cohort. Oligogenicity may explain the genetic basis of disease in many DH patients. Functional studies and further clinical studies with larger DH patient cohorts are needed to validate the roles of the mutations identified in this study.

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