Article
Oncology
Chun-Ting Hu, Jing-Long Wang, Ting Hou, Zhao-Wen Yan, Li-Dong Zu, Guo-Hui Fu, Wei-Wei Shen
Summary: This study demonstrates discrepancies in the genomic profiles between primary tumors and metastases, especially between liver and lung metastases. The coincidence rate of primary tumors and metastases is 51.8%, with lung metastases showing a significantly higher rate than liver metastases. Furthermore, the number of specific mutations differs between primary tumors, liver metastases, and lung metastases, indicating a possible polyclonal seeding mechanism for liver metastases.
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
(2023)
Article
Genetics & Heredity
Akifumi Nozawa, Akihiro Fujino, Shunsuke Yuzuriha, Souichi Suenobu, Aiko Kato, Fumiaki Shimizu, Noriko Aramaki-Hattori, Kanako Kuniyeda, Kazuya Sakaguchi, Hidenori Ohnishi, Yoko Aoki, Michio Ozeki
Summary: Recent studies have revealed the importance of the PI3K signaling pathway in the pathogenesis of slow-flow vascular malformations (SFVMs). Genetic analysis may provide insights into the mechanisms involved in SFVM pathogenesis and identify potential therapeutic targets.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Yu Jeong Choi, Hongkyung Kim, Won Kee Ahn, Seung-Tae Lee, Jung Woo Han, Jong Rak Choi, Chuhl Joo Lyu, Seungmin Hahn, Saeam Shin
Summary: Hereditary hemolytic anemia (HHA) is a group of genetic disorders characterized by the destruction of circulating red blood cells. Incorporation of next-generation sequencing (NGS) has proven to be a valuable tool in the diagnostic process of HHA.
BMC MEDICAL GENOMICS
(2023)
Article
Biotechnology & Applied Microbiology
Dandan Wang, Kai Ma, Wei Deng, Jingyu Li, Shaohua Xiang, Yang Zhang, Ying Fu, Heng Dai, Bingding Huang
Summary: This study developed a custom-targeted NGS panel for accurately detecting various genomic alterations in cancer patients, providing strong support for guiding targeted therapy decisions.
ONCOTARGETS AND THERAPY
(2021)
Article
Genetics & Heredity
Yunlong Li, Jie Su, Jingman Zhang, Jiahong Pei, Dongmei Li, Yinhong Zhang, Jingyu Li, Menglang Chen, Baosheng Zhu
Summary: This study used targeted next-generation sequencing to identify pathogenic mutations in 84 deaf patients in southwestern China. Common and novel causative genes were found, highlighting the importance of further studying the spectrum of deafness genes in this region.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Claudia Maria Hattinger, Chiara Casotti, Maria Pia Patrizio, Silvia Luppi, Leonardo Fantoni, Katia Scotlandi, Toni Ibrahim, Massimo Serra
Summary: This study investigated the relationship between SNPs and CDDP resistance in high-grade osteosarcoma cells, providing a basis for further research on the topic.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sanjay Joshi, Hadia Awan, Priyanka Paul, Ran Tian, Sharyn E. Perry
Summary: AGL15, a member of the MADS-domain transcription factor family, primarily accumulates in plant embryos and promotes plant regeneration. Through the use of different technological platforms, researchers have identified an interaction between AGL15 and the brassinosteroid hormone signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Juan A. Santamaria-Barria, Chikako Matsuba, Adam Khader, Anthony J. Scholar, Mary Garland-Kledzik, Trevan D. Fischer, Richard Essner, Matthew P. Salomon, Joshua M. V. Mammen, Melanie Goldfarb
Summary: This study analyzed melanoma samples and identified age-related mutational differences, as well as potential targetable mutations for personalized therapies.
JOURNAL OF SURGICAL ONCOLOGY
(2023)
Review
Biochemical Research Methods
Surui Pei, Tao Liu, Xue Ren, Weizhong Li, Chongjian Chen, Zhi Xie
Summary: DNA variants are important sources of genetic variation among individuals. Next-generation sequencing (NGS) and third-generation sequencing (TGS) technologies are widely used for genome-wide variant calling. Different variant callers show varying performance on NGS and TGS data, with TGS detecting more variants, particularly in complex and repetitive regions. Careful selection of tools and parameters is essential for accurate variant calling under different scenarios.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Pharmacology & Pharmacy
Chiara Casotti, Claudia Maria Hattinger, Maria Pia Patrizio, Silvia Luppi, Leonardo Fantoni, Michela Pasello, Katia Scotlandi, Toni Ibrahim, Massimo Serra
Summary: In this study, an innovative mmNGS approach was used to investigate SNPs associated with MTX resistance in HGOS cell lines. The results showed that allele changes in TP53, SLC19A1, and MTHFR were functionally involved in the development of MTX resistance. In addition, a fusion transcript of DHFR and MSH3 was identified in the cells with the highest MTX resistance level.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
You-Kang Chang, Hui-Hwa Tseng, Chung-Man Leung, Kuo-Cheng Lu, Kuo-Wang Tsai
Summary: This study investigates the relationship between oncogenic and tumor-suppressive gene mutations and the outcomes of patients with rectal carcinoma receiving neoadjuvant chemoradiotherapy (nCRT). The results suggest that mutations in BRAF, SMAD4, and TP53 genes may be associated with the response to nCRT in patients with rectal adenocarcinoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Bettina Winzeler, Nicola Tufton, Eugenie Lim, Ben G. Challis, Soo-Mi Park, Louise Izatt, Paul Carroll, Anand Velusamy, Tony Hulse, Benjamin C. Whitelaw, Ezequiel Martin, Fay Rodger, Melanie Maranian, Graeme R. Clark, Scott Akker, Eamonn R. Maher, Ruth T. Casey
Summary: This study investigated the clinical utility of somatic sequencing in a large cohort of patients with PPGL in the United Kingdom, finding that 32% of patients had a germline mutation and 26% had one or more driver somatic variants. Pathogenic somatic variants were most commonly identified in the VHL, NF1, HRAS, and RET genes, and somatic sequencing may be most informative for patients without a germline genetic driver.
CLINICAL ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Athanasia Stoupa, Ghada Al Hage Chehade, Rim Chaabane, Dulanjalee Kariyawasam, Gabor Szinnai, Sylvain Hanein, Christine Bole-Feysot, Cecile Fourrage, Patrick Nitschke, Caroline Thalassinos, Graziella Pinto, Mouna Mnif, Sabine Baron, Marc De Kerdanet, Rachel Reynaud, Pascal Barat, Mongia Hachicha, Neila Belguith, Michel Polak, Aurore Carre
Summary: In this study, targeted next-generation sequencing was used to study a cohort of 19 well-characterized patients with Congenital Hypothyroidism and Dyshormonogenesis, identifying likely disease-causing mutations in 53% of patients, with TG mutations being the most common genetic defect. Targeted next-generation sequencing provides a rapid and cost-effective genetic diagnosis in patients with Congenital Hypothyroidism due to Dyshormonogenesis.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Genetics & Heredity
Alesa Kristan, Tadej Pajic, Ales Maver, Tadeja Rezen, Tanja Kunej, Rok Kolic, Andrej Vuga, Martina Fink, Spela Zula, Helena Podgornik, Sasa Anzej Doma, Irena Preloznik Zupan, Damjana Rozman, Natasa Debeljak
Summary: An erythrocytosis is characterized by an increase in red blood cell mass, often associated with genetic variants in genes related to oxygen sensing, hematopoietic cell maturation, and oxygen transfer. Classical sequencing approaches may only provide a correct diagnosis for a fraction of patients with congenital erythrocytosis, as the genetic background of the disorder is more complex and involves additional genes. A targeted next-generation sequencing approach was used in this study to identify genetic variants in patients with unexplained erythrocytosis, leading to the discovery of pathogenic and novel variants in relevant genes, as well as the identification of potential associations with iron metabolism genes. This study contributes to improving the diagnosis and management of Slovenian patients with erythrocytosis and provides insights for future research into the etiology of this rare hematological disorder.
FRONTIERS IN GENETICS
(2021)
Article
Medicine, General & Internal
Jin Hyuk Choi, Jesang Yu, Minjung Jung, Junyong Jekal, Ku Sang Kim, Sung Ui Jung
Summary: This study analyzed the correlation between somatic mutations in breast cancer, analyzed using NGS, and the prognosis of patients. TP53 and PIK3CA mutations were found to be potentially associated with the prognosis of breast cancer. These findings have implications for predicting the prognosis of breast cancer.
Article
Genetics & Heredity
Alexander J. Thompson, Yousef M. Alwan, Vijay A. C. Ramani, D. Gareth Evans, Eamonn R. Maher, Emma R. Woodward
Summary: The purpose of this study was to determine the cost-effectiveness of annual renal imaging surveillance (RIS) in hereditary leiomyomatosis and renal cell cancer (HLRCC). The study found that annual contrast-enhanced renal MRI surveillance (CERMRIS) in HLRCC is cost-effective across different age groups.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
Helen Hanson, Miranda Durkie, Fiona Lalloo, Louise Izatt, Terri P. McVeigh, Jackie A. Cook, Carole Brewer, James Drummond, Samantha Butler, Treena Cranston, Ruth Casey, Tricia Tan, Daniel Morganstein, Diana M. Eccles, Marc Tischkowitz, Clare Turnbull, Emma Roisin Woodward, Eamonn R. Maher
Summary: SDHA PGV carriers are common in patients with paraganglioma and phaeochromocytoma, and the variant often presents as sporadic tumors in patients without family history. Studies show that the penetrance of SDHA-associated tumors is low, which poses challenges for surveillance and management.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
Helen Hanson, Anjana Kulkarni, Lucy Loong, Grace Kavanaugh, Bethany Torr, Sophie Allen, Munaza Ahmed, Antonis C. Antoniou, Ruth Cleaver, Tabib Dabir, D. Gareth Evans, Ellen Golightly, Rosalyn Jewell, Kelly Kohut, Ranjit Manchanda, Alex Murray, Jennie Murray, Kai-Ren Ong, Adam N. Rosenthal, Emma Roisin Woodward, Diana M. Eccles, Clare Turnbull, Marc Tischkowitz, Fiona Lalloo
Summary: This paper presents a summary of the process and key recommendations from a national consensus on the clinical management of BRIP1, PALB2, RAD51D, and RAD51C carriers.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
D. Gareth Evans, Siva Sithambaram, Elke Maria van Veen, George J. Burghel, Helene Schlecht, Elaine F. Harkness, Helen Byers, Jamie M. Ellingford, Ashu Gandhi, Sacha J. Howell, Anthony Howell, Claire Forde, Fiona Lalloo, William G. Newman, Miriam Jane Smith, Emma Roisin Woodward
Summary: This study aimed to investigate the frequency of germline pathogenic variants (PVs) in women with ductal carcinoma in situ (DCIS) and grade 1 invasive breast cancer (G1BC). The results showed that DCIS was more likely to be associated with both BRCA1/2 and non-BRCA1/2 PVs than G1BC. Extended panel testing is recommended for young-onset DCIS where PV detection rates are highest.
JOURNAL OF MEDICAL GENETICS
(2023)
Letter
Oncology
D. Gareth Evans, Emma R. Woodward
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Jose Garcia-Pelaez, Rita Barbosa-Matos, Silvana Lobo, Alexandre Dias, Luzia Garrido, Sergio Castedo, Sonia Sousa, Hugo Pinheiro, Liliana Sousa, Rita Monteiro, Joaquin J. Maqueda, Susana Fernandes, Fatima Carneiro, Nadia Pinto, Carolina Lemos, Carla Pinto, Manuel R. Teixeira, Stefan Aretz, Svetlana Bajalica-Lagercrantz, Judith Balmana, Ana Blatnik, Patrick R. Benusiglio, Maud Blanluet, Vincent Bours, Hilde Brems, Joan Brunet, Daniele Calistri, Gabriel Capella, Sergio Carrera, Chrystelle Colas, Karin Dahan, Robin de Putter, Camille Desseignes, Elena Dominguez-Garrido, Conceicao Egas, D. Gareth Evans, Damien Feret, Eleanor Fewings, Rebecca C. Fitzgerald, Florence Coulet, Maria Garcia-Barcina, Maurizio Genuardi, Lisa Golmard, Karl Hackmann, Helen Hanson, Elke Holinski-Feder, Robert Huneburg, Mateja Krajc, Kristina Lagerstedt-Robinson, Conxi Lazaro, Marjolijn J. L. Ligtenberg, Cristina Martinez-Bouzas, Sonia Merino, Genevieve Michils, Srdjan Novakovic, Ana Patino-Garcia, Guglielmina Nadia Ranzani, Evelin Schrock, Ines Silva, Catarina Silveira, Jose L. Soto, Isabel Spier, Verena Steinke-Lange, Gianluca Tedaldi, Maria-Isabel Tejada, Emma R. Woodward, Marc Tischkowitz, Nicoline Hoogerbrugge, Carla Oliveira
Summary: This study analyzed families carrying rare CDH1 variants, comparing the cancer spectrum in carriers of pathogenic or likely pathogenic variants (PV/LPV) or missense variants of unknown significance, and evaluated the performance of expanded criteria for CDH1 testing. The results showed that PV/LPV carriers were positively associated with lobular breast cancer, diffuse gastric cancer, and gastric cancer, while missense variants of unknown significance did not show this positive association.
Article
Endocrinology & Metabolism
Sara Mellid, Eduardo Gil, Rocio Leton, Eduardo Caleiras, Emiliano Honrado, Susan Richter, Nuria Palacios, Marcos Lahera, Juan C. Galofre, Adria Lopez-Fernandez, Maria Calatayud, Aura D. Herrera-Martinez, Maria A. Galvez, Xavier Matias-Guiu, Milagros Balbin, Esther Korpershoek, Eugenie S. Lim, Francesca Maletta, Sofia Lider, Stephanie M. J. Fliedner, Nicole Bechmann, Graeme Eisenhofer, Letizia Canu, Elena Rapizzi, Irina Bancos, Mercedes Robledo, Alberto Cascon
Summary: In recent years, it has been found that a significant percentage of PPGL patients carry known germline mutations in susceptibility genes. Furthermore, some patients with mutations in the NF1 gene also have co-occurring mutations in other PPGL related genes, which may play a role in tumor development.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Robert D. D. Morgan, George J. J. Burghel, Nicola Flaum, Michael Bulman, Philip Smith, Andrew R. R. Clamp, Jurjees Hasan, Claire L. L. Mitchell, Zena Salih, Emma R. R. Woodward, Fiona Lalloo, Emma J. J. Crosbie, Richard J. J. Edmondson, Helene Schlecht, Gordon C. C. Jayson, D. Gareth R. Evans
Summary: Approximately 15% of patients diagnosed with high-grade non-mucinous epithelial ovarian cancer (EOC) have a germline BRCA1/2 mutation, with somatic mutations occurring more frequently in patients aged >= 80. Germline BRCA1/2 testing in this age group can be reserved for those with a detectable tumour BRCA1/2 mutation. Testing for tumour BRCA1/2 and homologous recombination deficiency is sufficient for patients aged >= 80 with non-mucinous high-grade EOC.
Review
Genetics & Heredity
Fiona Jane Bruinsma, James G. Dowty, Aung Ko Win, Laura C. Goddard, Prachi Agrawal, Domenico Attina', Nabil Bissada, Monica De Luise, Daniel B. Eisen, Mitsuko Furuya, Giuseppe Gasparre, Maurizio Genuardi, Anne-Marie Gerdes, Thomas Van Overeem Hansen, Arjan C. Houweling, Paul Christiaan Johannesma, Andre Lencastre, Derek Lim, Noralane M. Lindor, Valentina Luzzi, Maeve Lynch, Antonella Maffe, Fred H. Menko, Guido Michels, Jose S. Pulido, Ryu H. Jay, Elke C. Sattler, Ortrud K. Steinlein, Sara Tomassetti, Kathy Tucker, Daniela Turchetti, Irma van de Beek, Lore van Riel, Maurice van Steensel, Thierry Zenone, Maurizo Zompatori, Jennifer Walsh, Davide Bondavalli, Eamonn R. Maher, Ingrid M. Winship
Summary: BHD syndrome is a rare genetic syndrome caused by FLCN gene variants, which can increase the risk of various manifestations including fibrofolliculomas, pulmonary cysts, pneumothorax, and renal cell carcinoma. This study provides updated penetrance estimates based on a large dataset, which are crucial for the genetic counseling and clinical management of BHD syndrome.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
D. Gareth Evans, George J. Burghel, Helene Schlecht, Elaine F. Harkness, Ashu Gandhi, Sacha J. Howell, Anthony Howell, Claire Forde, Fiona Lalloo, William G. Newman, Miriam Jane Smith, Emma Roisin Woodward
Summary: This study aimed to investigate the frequency of germline pathogenic variants (PVs) in women with bilateral breast cancer. BRCA1/2 and CHEK2 c.1100delC molecular analysis were conducted in 764 samples, and a multigene panel was performed in 156 samples. The detection rates of PVs were assessed according to age at first primary, Manchester Score, and breast pathology. The results showed high rates of detection of BRCA1 and BRCA2 PVs in triple negative and grade 3 ER+HER2- first primary diagnoses, respectively. The study also found that the ER status of the first primary strongly predicted the ER status of the second contralateral tumor in BRCA1/2 patients.
JOURNAL OF MEDICAL GENETICS
(2023)
Review
Endocrinology & Metabolism
Alberto Cascon, Bruna Calsina, Maria Monteagudo, Sara Mellid, Alberto Diaz-Talavera, Maria Curras-Freixes, Mercedes Robledo
Summary: The genetics of pheochromocytoma and paraganglioma (PPGL) has become increasingly complex over the last two decades, with more than 20 driver genes implicated in the disease. However, a significant percentage of patients still lack a genetic diagnosis. Mutations in known PPGL genes deregulate three main signaling pathways, providing potential targets for personalized treatment. Integrating results from genomic platforms allows for the discovery of regulatory mechanisms and the potential for precision medicine in metastatic PPGL patients.
JOURNAL OF MOLECULAR ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Bruna Calsina, Elena Pineiro-Yanez, Angel M. Martinez-Montes, Eduardo Caleiras, Angel Fernandez-Sanroman, Maria Monteagudo, Rafael Torres-Perez, Coral Fustero-Torre, Marta Pulgarin-Alfaro, Eduardo Gil, Rocio Leton, Scherezade Jimenez, Santiago Garcia-Martin, Maria Carmen Martin, Juan Maria Roldan-Romero, Javier Lanillos, Sara Mellid, Maria Santos, Alberto Diaz-Talavera, Angeles Rubio, Patricia Gonzalez, Barbara Hernando, Nicole Bechmann, Margo Dona, Maria Calatayud, Sonsoles Guadalix, Cristina Alvarez-Escola, Rita M. Regojo, Javier Aller, Maria Isabel Del Olmo-Garcia, Adria Lopez-Fernandez, Stephanie M. J. Fliedner, Elena Rapizzi, Martin Fassnacht, Felix Beuschlein, Marcus Quinkler, Rodrigo A. Toledo, Massimo Mannelli, Henri J. Timmers, Graeme Eisenhofer, Sandra Rodriguez-Perales, Orlando Dominguez, Geoffrey Macintyre, Maria Curras-Freixes, Cristina Rodriguez-Antona, Alberto Cascon, Luis J. Leandro-Garcia, Cristina Montero-Conde, Giovanna Roncador, Juan Fernando Garcia-Garcia, Karel Pacak, Fatima Al-Shahrour, Mercedes Robledo
Summary: The mechanisms of metastasis in pheochromocytoma/paraganglioma (mPPGL) are unknown. Genomic and immunogenomic profiling of mPPGL tumors reveal potential biomarkers for risk of metastasis and immunotherapy response.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Larissa Bilo, Eguzkine Ochoa, Sunwoo Lee, Daniela Dey, Ingo Kurth, Florian Kraft, Fay Rodger, France Docquier, Ana Toribio, Leonardo Bottolo, Gerhard Binder, Gyoergy Fekete, Miriam Elbracht, Eamonn R. Maher, Matthias Begemann, Thomas Eggermann
Summary: Imprinting disorders (ImpDis) are caused by aberrant regulation of monoallelically and parent-of-origin-dependent expressed genes. This study aimed to investigate multilocus imprinting disturbances (MLIDs) in ImpDis patients using methylation data obtained from next-generation sequencing (ImprintSeq) and whole-exome sequencing (WES). The results showed that ImprintSeq has higher sensitivity in detecting mosaic imprinting defects in MLID patients, while WES failed to identify additional MLID causes.
CLINICAL EPIGENETICS
(2023)
Article
Medicine, Research & Experimental
Ellen Colvin, Stephanie Ng, John Hepworth, Janice Hepworth, Thomas Hartley, Nicola Godfrey, Karen Tricker, Jeanette Rothwell, Glenda Beaman, Emma R. Woodward
Summary: To ensure patient-led translational outcomes and meet patient needs, patient and public involvement (PPI) should be embedded within clinical research. Active partnerships with patient and public groups provide an important opportunity to understand patient needs and inform future research. In this study, a hereditary renal cancer (HRC) PPI group was developed, involving patients, public participants, researchers, and healthcare professionals. The participants collaboratively developed a novel patient information sheet for HRC patients to aid communication with family members regarding diagnoses and wider implications.
JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE
(2023)