Anna M Armitage, Monica A Kundra, Neda Ghiam, Paldeep S Atwal, Dayna Morel, Kathleen S Hruska, Rebecca Torene, Irman Forghani
We report the first case of blood chimerism involving a pathogenic RB1 variant in naturally conceived monochorionic-dizygotic twins (MC/DZ) with the twin-twin-transfusion syndrome (TTTS), presumably caused by the exchange of stem-cells. Twin A developed bilateral retinoblastoma at 7 months of age. Initial genetic testing identified a de novo RB1 pathogenic variant, with a 20% allelic ratio in both twins' blood. Subsequent genotyping of blood and skin confirmed dizygosity, with the affected twin harboring the RB1 pathogenic variant in skin and blood, and the unaffected twin carrying the variant only in blood...
October 9, 2020: American Journal of Medical Genetics. Part A
Elisa Gelli, Chiara Fallerini, Floriana Valentino, Annarita Giliberti, Francesca Castiglione, Lucrezia Laschi, Maria Palmieri, Alessandra Fabbiani, Rossella Tita, Maria Antonietta Mencarelli, Alessandra Renieri, Francesca Ariani
Malignant ovarian germ cell tumors (MOGCTs) are neoplasms of the ovary, of which, due to their rarity and heterogeneity, few is reported about genetic background and development. Here, we report a 18-years old patient diagnosed with an ovarian mixed germ cell tumor, without any previous history of malignancies, who has been treated with surgery and chemotherapy and died 4 years later due to peritoneal metastasis complications. Patient's blood DNA was screened for a panel of 52 cancer-related genes in order to identify predisposing aberrations to this rare cancer...
2020: Frontiers in Oncology
Chunsik Lee, Jong Kyong Kim
Retinoblastoma (RB) is a pediatric ocular tumor mostly occurring due to the biallelic loss of RB1 gene in the developing retina. Early studies of genomic aberrations in RB have provided a valuable insight into how RB can progress following the tumor-initiating RB1 mutations and have established a notion that inactivation of RB1 gene is critical to initiate RB but this causative genetic lesion alone is not sufficient for malignant progression. With the advent of high-throughput sequencing technologies, we now have access to the comprehensive genomic and epigenetic landscape of RB and have come to appreciate that RB tumorigenesis requires both genetic and epigenetic alterations that might be directly or indirectly driven by RB1 loss...
August 25, 2020: Journal of Cellular Physiology
M Ashwin Reddy, Mussa Butt, Anne-Marie Hinds, Catriona Duncan, Elizabeth A Price, Mandeep S Sagoo, Zerrin Onadim
OBJECTIVE: To compare the number of tumors per eye for mosaic carriers of RB1 pathogenic variants with full germline variants and the conversion from unilateral to bilateral disease. DESIGN: Retrospective cohort study comparing patients with retinoblastoma and different genetic subtypes (HP: high penetrant, LP: low penetrant & mosaicism). SUBJECTS: Data were analysed between 1992 and 2018 at the Retinoblastoma Unit, Royal London Hospital, London UK...
August 21, 2020: Ophthalmology Retina
Qin Wu, Wail Ba-Alawi, Genevieve Deblois, Jennifer Cruickshank, Shili Duan, Evelyne Lima-Fernandes, Jillian Haight, Seyed Ali Madani Tonekaboni, Anne-Marie Fortier, Hellen Kuasne, Trevor D McKee, Hassan Mahmoud, Michelle Kushida, Sarina Cameron, Nergiz Dogan-Artun, WenJun Chen, Yan Nie, Lan Xin Zhang, Ravi N Vellanki, Stanley Zhou, Panagiotis Prinos, Bradly G Wouters, Peter B Dirks, Susan J Done, Morag Park, David W Cescon, Benjamin Haibe-Kains, Mathieu Lupien, Cheryl H Arrowsmith
Triple negative breast cancer (TNBC) is a deadly form of breast cancer due to the development of resistance to chemotherapy affecting over 30% of patients. New therapeutics and companion biomarkers are urgently needed. Recognizing the elevated expression of glucose transporter 1 (GLUT1, encoded by SLC2A1) and associated metabolic dependencies in TNBC, we investigated the vulnerability of TNBC cell lines and patient-derived samples to GLUT1 inhibition. We report that genetic or pharmacological inhibition of GLUT1 with BAY-876 impairs the growth of a subset of TNBC cells displaying high glycolytic and lower oxidative phosphorylation (OXPHOS) rates...
August 21, 2020: Nature Communications
Kritika Krishnamurthy, Mike Cusnir, Michael Schwartz, Vathany Sriganeshan, Robert J Poppiti
BACKGROUND: Neuroendocrine carcinomas (NECs) arise from neuroendocrine cells present throughout the body, and often present with metastases even with small and undetectable primary tumors. Additionally, neuroendocrine differentiation can be seen in carcinomas of non-neuroendocrine origin further complicating the landscape of metastatic NECs. Organ specific immunohistochemical markers such as TTF1, CDX2 and PAX8 are often lost in high grade tumors and may be non-contributory in localizing the primary site...
September 2020: Pathology, Research and Practice
Rossukon Kaewkhaw, Duangnate Rojanaporn
Retinoblastoma is a retinal cancer that is initiated in response to biallelic loss of RB1 in almost all cases, together with other genetic/epigenetic changes culminating in the development of cancer. RB1 deficiency makes the retinoblastoma cell-of-origin extremely susceptible to cancerous transformation, and the tumor cell-of-origin appears to depend on the developmental stage and species. These are important to establish reliable preclinical models to study the disease and develop therapies. Although retinoblastoma is the most curable pediatric cancer with a high survival rate, advanced tumors limit globe salvage and are often associated with high-risk histopathological features predictive of dissemination...
August 16, 2020: Cancers
Anna C Dusenbery, Jonathan J Davick, Robin D LeGallo, Eli S Williams
Spindle cell lipomas/pleomorphic lipomas, mammary-type myofibroblastomas, and cellular angiofibromas are benign mesenchymal tumors that demonstrate histologically overlapping features but with varying anatomic locations and an uncertain etiologic relationship. These tumors have also been found to have an overlapping molecular profile with shared 13q14 deletions, which is the location of the tumor suppressor gene RB1 that encodes the retinoblastoma protein. Molecular studies thus far have largely focused on the RB1 locus, using primarily immunohistochemistry and fluorescence in situ hybridization to characterize RB1 status...
August 2020: Human Pathology
Sabine Dittner-Moormann, Madlen Reschke, Eva Biewald, Alma Kuechler, Barbara Klein, Beate Timmermann, Dietmar Lohmann, Petra Ketteler, Deniz Kanber
Background: Retinoblastoma is a malignancy of the eye in children characterized by biallelic inactivation of the retinoblastoma 1 gene ( RB1 ), located at chromosome 13q14.2. Children with interstitial chromosome 13q deletions that include the RB1 gene show a predisposition to develop retinoblastoma and variable other features. Large 13q deletions with severe clinical phenotype are nearly always the result of a de novo mutation, i.e. the pathogenic alteration is not detected in parents...
2020: Molecular Cytogenetics
Ioan Alexandru Florian, Teodora Larisa Timiș, Gheorghe Ungureanu, Ioan Stefan Florian, Adrian Bălașa, Ioana Berindan-Neagoe
BACKGROUND: Brain arteriovenous malformations (AVMs) are a relatively infrequent vascular pathology of unknown etiology that, despite their rarity, cause the highest number of hemorrhagic strokes under the age of 30 years. They pose a challenge to all forms of treatment due to their variable morphology, location, size, and, last but not least, evolving nature. MicroRNAs (miRNAs) are non-coding RNA strands that may suppress the expression of target genes by binding completely or partially to their complementary sequences...
July 28, 2020: Neurological Research
Prachi Kothari, Francesco Marass, Julie L Yang, Caitlin M Stewart, Dennis Stephens, Juber Patel, Maysun Hasan, Xiaohong Jing, Fanli Meng, Jeanette Enriquez, Kety Huberman, Agnes Viale, Jasmine H Francis, Michael F Berger, Neerav Shukla, David H Abramson, Ira J Dunkel, Dana W Y Tsui
PURPOSE: The enucleation rate for retinoblastoma has dropped from over 95% to under 10% in the past 10 years as a result of improvements in therapy. This reduces access to tumor tissue for molecular profiling, especially in unilateral retinoblastoma, and hinders the confirmation of somatic RB1 mutations necessary for genetic counseling. Plasma cell-free DNA (cfDNA) has provided a platform for noninvasive molecular profiling in cancer, but its applicability in low tumor burden retinoblastoma has not been shown...
July 7, 2020: Cancer Medicine
D Schofield, M J B Zeppel, S Staffieri, R N Shrestha, D Jelovic, E Lee, R V Jamieson
This study aimed to investigate the cost-effectiveness of preimplantation genetic diagnosis (PGD) for the reproductive choices of patients with heritable retinoblastoma. The study modelled the costs of three cycles of in-vitro fertilization (IVF) and PGD across all uptake rates of PGD, number of children affected with retinoblastoma at each uptake rate and the estimated quality-adjusted life years (QALYs) gained. Cost-effectiveness analysis was conducted from the Australian public healthcare perspective. The intervention was the use of three cycles (one fresh and two frozen) of IVF and PGD with the aim of live births unaffected by the retinoblastoma phenotype...
June 2020: Reproductive Biomedicine & Society Online
Medi Kori, Kazim Yalcin Arga
Oncogenic viruses are among the apparent causes of cancer-associated mortality. It was estimated that 12% to 15% of human malignancies are linked to oncoviruses. Although modernist strategies and traditional genetic studies have defined host-pathogen interactions of the oncoviruses, their host functions which are critical for the establishment of infection still remain mysterious. However, over the last few years, it has become clear that infections hijack and modify cellular pathways for their benefit. In this context, we constructed the virus-host protein interaction networks of seven oncoviruses (EBV, HBV, HCV, HTLV-1, HHV8, HPV16, and HPV18), and revealed cellular pathways hijacking as a result of oncogenic virus infection...
June 20, 2020: Biochimica et Biophysica Acta. Molecular Basis of Disease
Jianchang Li, Xiuming Liu, Wenqi Wang, Chaopeng Li
Introduction: Retinoblastoma (RB) is a malignant tumor that is derived from photoreceptors. It is common in children under 3 years old with a family genetic predisposition. MicroRNA-133a-3p (miR-133a-3p) is one of the tumor-related miRNAs that interprets a critical function in the genesis and development of various tumors. This study investigated the effects and underlying mechanisms of miR-133a-3p in RB. Material and methods: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis was used to assess the miR-133a-3p expression in RB tissues and a cell model...
2020: Archives of Medical Science: AMS
Kaitlyn Flegg, Maxwell J Gelkopf, Sarah A Johnson, Helen Dimaras
BACKGROUND: Retinoblastoma is a childhood cancer of the eye that can have lifelong effects on patients and families. The purpose of this study was for people affected by retinoblastoma, clinicians and researchers to jointly determine the top 10 retinoblastoma research priorities in Canada. METHODS: An adaptation of the James Lind Alliance Priority Setting Partnership (PSP) methodology was employed. People were invited to participate in any stage of the priority-setting process if they were a resident of Canada, and were a patient with retinoblastoma (or a family member or friend of someone diagnosed with retinoblastoma) or a clinician or researcher interested in retinoblastoma...
April 2020: CMAJ Open
Yukun Mao, Qingbin Nie, Yang Yang, Gengsheng Mao
Retinoblastoma is a common intraocular malignant tumor in children. However, the molecular and genetic mechanisms of retinoblastoma remain unclear. The gene expression dataset GSE110811 was retrieved from Gene Expression Omnibus. After preprocessing, coexpression modules were constructed by weighted gene coexpression network analysis (WGCNA), and modules associated with clinical traits were identified. In addition, functional enrichment analysis was performed for genes in the indicated modules, and protein‑protein interaction (PPI) networks and subnetworks were constructed based on these genes...
May 27, 2020: Molecular Medicine Reports
Yacoub A Yousef, Abdelrahman Alkhoms, Reem AlJabari, Mays AlJboor, Mona Mohammad, Maha Lahlouh, Rasha Deebajah, Hadeel Halalsheh, Maysa Al-Hussaini, Imad Jaradat, Munir Shawagfeh, Iyad Sultan, Mustafa Mehyar, Ibrahim AlNawaiseh
Purpose : To study the impact of a Retinoblastoma (Rb) screening program in the absence of genetic testing on the management and outcome of high-risk children. Methods : This is a retrospective, clinical case series of 76 children from families involved in a Rb screening program as they had higher than normal risk as calculated by the conventional ways without genetic testing. Data included calculated risk, method of diagnosis, demographics, tumor features, treatment modalities, and management outcome. Results : Out of the 76 children screened, 46 children were diagnosed with Rb (12 by screening and 34 had signs of Rb), the other 30 were free of disease...
May 20, 2020: Ophthalmic Genetics
Xin Liu, Shuying Shang, Weiwei Chu, Liang Ma, Chenxin Jiang, Yanping Ding, Jianlin Wang, Shengxiang Zhang, Baoping Shao
OBJECTIVES: Ageing is a universal and gradual process of organ deterioration. Radiation induces oxidative stress in cells, which leads to genetic damage and affects cell growth, differentiation and senescence. Astragaloside (AS)-IV has antioxidative, anti-apoptotic and anti-inflammatory properties. METHODS: To study the protective mechanism of AS-IV on radiation-induced brain cell senescence, we constructed a radiation-induced brain cell ageing model, using biochemical indicators, senescence-associated galactosidase (SA-β-gal) senescence staining, flow cytometry and Western blotting to analyse the AS-IV resistance mechanism to radiation-induced brain cell senescence...
May 15, 2020: Journal of Pharmacy and Pharmacology
Wei Xiao, Xian Ji, Huijing Ye, Huiqi Zeng, Yang Gao, Rongxin Chen, Xiaoyun Chen, Yuxiang Mao, Huasheng Yang
Purpose: To evaluate parent knowledge of screening and genetic testing for retinoblastoma and its potential correlation with demographics, clinical features, and socioeconomical factors. Methods: It was a cross-sectional study conducted at the ocular oncology unit of a tertiary ophthalmic center in Southern China. A face-to-face interview was administered to parents of retinoblastoma children during hospitalization. Parent knowledge was assessed using the sum score of a 7-item questionnaire...
2020: Journal of Ophthalmology
Adebola Enikanolaiye, Julie Ruston, Rong Zeng, Christine Taylor, Marijke Schrock, Christie M Buchovecky, Jay Shendure, Elif Acar, Monica J Justice
Mutations in X-linked methyl-CpG-binding protein 2 ( MECP2) cause Rett syndrome (RTT). To identify functional pathways that could inform therapeutic entry points, we carried out a genetic screen for secondary mutations that improved phenotypes in Mecp2 /Y mice after mutagenesis with N -ethyl- N -nitrosourea (ENU). Here, we report the isolation of 106 founder animals that show suppression of Mecp2 -null traits from screening 3177 Mecp2 /Y genomes. Whole-exome sequencing, genetic crosses, and association analysis identified 22 candidate genes...
April 2020: Genome Research
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