Article
Oncology
Daniele Fanale, Alessia Fiorino, Lorena Incorvaia, Alessandra Dimino, Clarissa Filorizzo, Marco Bono, Daniela Cancelliere, Valentina Calo, Chiara Brando, Lidia Rita Corsini, Roberta Sciacchitano, Luigi Magrin, Alessia Pivetti, Erika Pedone, Giorgio Madonia, Alessandra Cucinella, Giuseppe Badalamenti, Antonio Russo, Viviana Bazan
Summary: The study found that around 10-20% of breast/ovarian cancer patients in Southern Italy carry germline BRCA1/2 VUS. Most patients are BRCA-w.t., with a small percentage carrying BRCA1/2 VUS, and some carrying BRCA1/2 pathogenic/likely pathogenic variants. Understanding the clinical significance of these VUS could potentially improve the identification of high-risk variants for clinical management of patients and their families in the future.
FRONTIERS IN ONCOLOGY
(2021)
Article
Genetics & Heredity
Htoo A. Wai, Matthew Constable, Cosima Drewes, Ian C. Davies, Eliska Svobodova, Esther Dempsey, Anand Saggar, Tessa Homfray, Sahar Mansour, Sofia Douzgou, Kate Barr, Stephanie Scott, David Hunt, Andrew G. L. Douglas, Diana Baralle
Summary: This study presents a short amplicon RT-PCR method for the detection of genes with low expression in blood. The method allows for the analysis of splicing events in genes with low TPM and can be used for clinical diagnostics.
Article
Biochemistry & Molecular Biology
Mudassar Ali Khan, M. Quadir Siddiqui, Ekaterina Kuligina, Ashok K. Varma
Summary: The BRCA2 Arg2502Cys mutation perturbs the structural integrity and conformational dynamics of BRCA2, decreasing the alpha-helical/beta-sheet propensity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Pathology
Anna Jasiak, Magdalena Koczkowska, Maciej Stukan, Dariusz Wydra, Wojciech Biernat, Ewa Izycka-Swieszewska, Kamil Buczkowski, Michael R. Eccles, Logan Walker, Bartosz Wasag, Magdalena Ratajska
Summary: The study aimed to determine the frequency of aberrant splicing in BRCA1 and BRCA2 genes in blood RNA extracted from ovarian cancer patients who were previously found negative for pathogenic alterations in 25 commonly analysed ovarian cancer genes. PCR, gel electrophoresis, Sanger sequencing, and RT-qPCR were used to analyze the frequency and spectrum of splicing alterations in BRCA1 and BRCA2 genes in 101 ovarian cancer patients and 80 healthy controls. The study found no novel pathogenic splicing alterations but identified six naturally occurring transcripts, of which three were significantly higher expressed in the ovarian cancer cohort than in healthy controls.
EXPERIMENTAL AND MOLECULAR PATHOLOGY
(2023)
Article
Oncology
Aniko Bozsik, Janos Papp, Vince Kornel Grolmusz, Attila Patocs, Edit Olah, Henriett Butz
Summary: This study investigated the functional characteristics of five uninvestigated variants with potential splice-modifying effect in genetically tested hereditary breast and ovarian cancer patients. The results provided evidence to reclassify two variants as likely pathogenic, one as a strong VUS, and one as likely benign. Additionally, the study reinforced the likely pathogenic assertion of a previously unreported variant based on its spliceogenic property and tumor LOH. However, one variant failed to present aberrant splicing despite suggestive predictions.
CANCER RESEARCH AND TREATMENT
(2022)
Review
Oncology
Daniele Fanale, Alessia Pivetti, Daniela Cancelliere, Antonio Spera, Marco Bono, Alessia Fiorino, Erika Pedone, Nadia Barraco, Chiara Brando, Alessandro Perez, Maria Francesca Guarneri, Tancredi Didier Bazan Russo, Salvatore Vieni, Girolamo Guarneri, Antonio Russo, Viviana Bazan
Summary: This review provides a comprehensive overview of literature studies concerning VUSs, in order to assess their impact on the population and provide new insight useful for appropriate patient management in clinical practice.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Article
Oncology
Giovanna Barbero, Roberta Zuntini, Pamela Magini, Laura Desiderio, Michela Bonaguro, Anna Myriam Perrone, Daniela Rubino, Mina Grippa, Antonio De Leo, Claudio Ceccarelli, Lea Godino, Sara Miccoli, Simona Ferrari, Donatella Santini, Pierandrea De Iaco, Claudio Zamagni, Giovanni Innella, Daniela Turchetti
Summary: Ovarian cancer is a highly lethal malignancy and genetic defects, including BRCA1 and BRCA2 alterations, are common in patients. A comprehensive study of 30 ovarian cancer patients revealed that 23% had BRCA alterations detectable by clinical testing, while 17% showed epigenetic silencing of BRCA1 in the tumor. Patients with BRCA deficit had greater genomic instability but better survival compared to those without BRCA deficit.
Review
Genetics & Heredity
Felicia Adam, Muriel Fluri, Amina Scherz, Manuela Rabaglio
Summary: The implementation of multigene panels for hereditary tumor syndrome has been increasing. This study aimed to determine the prevalence of VUS in patients with suspected Lynch syndrome and hereditary breast and ovarian cancer syndrome. The data showed that panel testing significantly increases VUS rates in non-BRCA genes.
BMC MEDICAL GENOMICS
(2023)
Letter
Oncology
Yun Liu, Honglian Wang, Xin Wang, Jiaqi Liu, Junjian Li, Xiang Wang, Yun Zhang, Zhigang Bai, Qinghua Zhou, Ying Wu, Yi Shen, Xiaoling Weng, Fatao Liu, Jiancheng Guo, Lijun Di, Olivier Gires, Zhongtao Zhang, Yiding Chen, Hongxia Wang
Summary: Accurate interpretation of BRCA1/2 variants is crucial for risk assessment and precise treatment of breast cancer. A study in a Chinese population identified 13 high-frequency pathogenic variants associated with specific characteristics in breast cancer patients. The findings provide rationale and sequencing information for tailored clinical risk assessment in the Chinese population.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mudassar Ali Khan, Ashok K. Varma
Summary: This study assessed the pathogenicity of Variant of Uncertain Significance (VUS) in the alpha-helical domain of h-BRCA2 through in silico tools and structure-based molecular dynamics simulation. The results showed that 18 variants were predicted to be pathogenic, and 12 mutations were found to have a destabilizing effect on the protein structure. Further analysis revealed that 5 variants may alter the folding pattern and require further validation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Oncology
Joanne Kotsopoulos, Shana J. Kim, Susan Armel, Louise Bordeleau, William D. Foulkes, Wendy McKinnon, Seema Panchal, Stephanie A. Cohen, Sophie Sun, Ping Sun, Larissa McKetton, Angela K. Troyer, Steven A. Narod
Summary: The study evaluated the impact of surgical, hormonal, and lifestyle factors on memory and attention in women with BRCA mutations. Results showed that women with preventive surgeries had higher cognitive assessment scores, reassuring high-risk women. However, further studies are needed to assess cognitive function over time as memory deficits become more prevalent.
Article
Oncology
Elena Bueno-Martinez, Lara Sanoguera-Miralles, Alberto Valenzuela-Palomo, Ada Esteban-Sanchez, Victor Lorca, Ines Llinares-Burguet, Jamie Allen, Alicia Garcia-Alvarez, Pedro Perez-Segura, Mercedes Duran, Douglas F. Easton, Peter Devilee, Maaike P. G. Vreeswijk, Miguel de la Hoya, Eladio A. Velasco-Sampedro
Summary: This study identified and classified spliceogenic ATM variants in the large-scale sequencing project BRIDGES, and found that many of these variants impaired splicing. The study also proposed a classification scheme based on mgATM data to assess the pathogenicity of ATM variants.
JOURNAL OF PATHOLOGY
(2022)
Article
Oncology
Hyeong In Ha, Eun Young Park, Kyung Jin Eoh, Yeon Jee Lee, Sang-Soo Seo, Sokbom Kang, Sang-Yoon Park, Myong Cheol Lim
Summary: This study investigated the clinical significance of the ovarian cancer cluster region (OCCR) in BRCA1 and BRCA2 genes. The results showed that patients with BRCA1 pathogenic variants (PVs) in the OCCR region had shorter progression-free survival (PFS) compared to those outside the OCCR. This trend was more pronounced in the platinum-sensitive subgroup. However, no significant differences were found in overall survival (OS) between patients with BRCA1/2 PVs, regardless of the variant location.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Oncology
Pascal Pujol, Kevin Yauy, Amandine Coffy, Nicolas Duforet-Frebourg, Sana Gabteni, Jean-Pierre Daures, Frederique Penault Llorca, Frederic Thomas, Kevin Hughes, Clare Turnbull, Virginie Galibert, Chloe Rideau, Carole Corsini, Laetitia Collet, Benoit You, David Genevieve, Nicolas Philippe
Summary: The meta-analysis revealed a higher prevalence of gBRCA2 in unselected breast cancer patients. Additionally, the majority of tumors in breast cancer patients with gBRCA are estrogen receptor-positive.
Article
Oncology
Chen Nahshon, Yakir Segev, Meirav Schmidt, Ofer Lavie
Summary: This study examines the attitudes of BRCA1/2 mutation carriers towards surgical risk reduction procedures. The results show high performance rates for risk reduction bilateral salpingo-oophorectomy, though hysterectomy was added in only 10% of cases. Additionally, only 33% of patients opted for risk reduction mastectomy, despite high awareness and acceptance rates. These findings provide important insights for clinicians counseling BRCA1/2 mutation carriers and highlight the need for personalized management plans.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2023)
Article
Genetics & Heredity
Dolors Casellas-Vidal, Irene Mademont-Soler, Joana Sanchez, Alberto Plaja, Neus Castells, Maria Camos, Javier Nieto-Moragas, Maria del Mar Garcia, Celia Rodriguez-Solera, Helena Rivera, Joan Brunet, Sara alvarez, Josep Perapoch, Xavier Queralt, Maria Obon
Summary: This study found that a deletion on chromosome X, including ZDHHC15, was present in three family members with ASD. Based on the results and gene data, ZDHHC15 is proposed as a candidate gene for ASD and may be associated with other neurodevelopmental disorders.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Oncology
Nuria Duenas, Matilde Navarro, Xavier Sanjuan, Nuria Ruiz, Silvia Iglesias, Xavier Matias-Guiu, Jordi Guardiola, Esther Kreisler, Sebastiano Biondo, Sara Gonzalez, Raquel Legido, Ana Blanco, Silvia Navarro, Leyre Asiain, Cristina Santos, Gabriel Capella, Marta Pineda, Joan Brunet
Summary: This study evaluates the yield of Lynch syndrome (LS) screening in colorectal cancer (CRC) in a single-referral centre and identifies the barriers to its effective implementation. LS suspected individuals were identified and underwent genetic analysis. Ten LS individuals were diagnosed, leading to cascade testing in their at-risk relatives.
CANCER EPIDEMIOLOGY
(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.
Review
Medicine, General & Internal
Charlotte Carton, D. Gareth Evans, Ignacio Blanco, Reinhard E. Friedrich, Rosalie E. Ferner, Said Farschtschi, Hector Salvador, Amedeo A. Azizi, Victor Mautner, Claas Roehl, Sirkku Peltonen, Stavros Stivaros, Eric Legius, Rianne Oostenbrink
Summary: This study aims to integrate information on NF1-associated tumors to assist healthcare professionals in tumor surveillance of NF1 individuals. Personalized and targeted tumor management proposals have been defined to ensure appropriate care for those in need.
Article
Biochemical Research Methods
Elisabet Munte, Lidia Feliubadalo, Marta Pineda, Eva Tornero, Maribel Gonzalez, Jose Marcos Moreno-Cabrera, Carla Roca, Joan Bales Rubio, Laura Arnaldo, Gabriel Capella, Jose Luis Mosquera, Conxi Lazaro
Summary: The study developed a software package called vaRHC to assist in variant classification in hereditary cancer. The package collects information from diverse databases and assigns or denies different types of evidence based on the latest international guidelines for specific genes or general criteria for other genes. It provides an automated variant classification using a Bayesian metastructure and considers CanVIG-UK recommendations, showing a better criteria assignment than a similar tool called Cancer SIGVAR. The source code of the package can be accessed on the GitHub repository and will be submitted to CRAN soon.
Article
Genetics & Heredity
Adria Lopez-Fernandez, Guillermo Villacampa, Monica Salinas, Elia Grau, Esther Darder, Estela Carrasco, Ares Solanes, Angela Velasco, Maite Torres, Elisabet Munte, Silvia Iglesias, Sara Torres-Esquius, Noemi Tuset, Orland Diez, Conxi Lazaro, Joan Brunet, Sergi Corbella, Judith Balmana
Summary: This study aims to analyze the psychological impact of genetic testing and to identify the profile of individuals at higher risk. Factors such as high neuroticism score, high baseline cancer worry, and a positive genetic test result were found to be independently associated with higher psychological impact. The highest risk profile consisted of women with high levels of neuroticism and a positive result. Uncertainty was mainly associated with high neuroticism levels, regardless of the genetic test result. A holistic approach to personalized genetic counseling should include the assessment of personality dimensions.
JOURNAL OF GENETIC COUNSELING
(2023)
Article
Genetics & Heredity
Nuria Duenas, Hannah Klinkhammer, Nuria Bonifaci, Isabel Spier, Andreas Mayr, Emadeldin Hassanin, Anna Diez-Villanueva, Victor Moreno, Marta Pineda, Carlo Maj, Gabriel Capella, Stefan Aretz, Joan Brunet
Summary: Polygenic risk scores (PRSs) have been used to stratify colorectal cancer (CRC) risk in the general population, but its role in Lynch syndrome (LS) is still conflicting. This study aimed to assess the ability of PRS to refine CRC risk prediction in European-descendant individuals with LS. The results showed that PRS was not significantly associated with CRC risk in the entire cohort, but it was slightly associated with an increased risk of CRC or advanced adenoma (AA) in individuals with early-onset disease.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
Laura Valle, Lior H. H. Katz, Andrew Latchford, Pilar Mur, Victor Moreno, Ian M. Frayling, Brandie Heald, Gabriel Capella
Summary: Constitutional pathogenic variants in the APC gene cause familial adenomatous polyposis, while APC c.3920T>A; p.Ile1307Lys (I1307K) is associated with a moderate increased risk of colorectal cancer (CRC), specifically in individuals of Ashkenazi Jewish descent. Different guidelines exist regarding genetic testing and clinical management for I1307K, due to inconclusive results in non-Ashkenazi populations. The International Society for Gastrointestinal Hereditary Tumors (InSiGHT) has generated a position statement on the APC I1307K allele to provide recommendations and address knowledge gaps.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Oncology
Alessio Cortellini, Josep Tabernero, Uma Mukherjee, Ramon Salazar, Anna Sureda, Clara Maluquer, Daniela Ferrante, Mark Bower, Rachel Sharkey, Oriol Mirallas, Andrea Plaja, Marc Cucurull, Ricard Mesia, Alessia Dalla Pria, Thomas Newsom-Davis, Mieke Van Hemelrijck, Ailsa Sita-Lumsden, Eleanor Apthorp, Bruno Vincenzi, Giuseppina Rita Di Fazio, Giuseppe Tonini, Francesco Pantano, Alexia Bertuzzi, Sabrina Rossi, Joan Brunet, Matteo Lambertini, Paolo Pedrazzoli, Federica Biello, Francesca D'Avanzo, Alvin J. X. Lee, Marianne Shawe-Taylor, Lucy Rogers, Cian Murphy, Lee Cooper, Ramis Andaleeb, Saira Khalique, Samira Bawany, Sarah Ahmed, M. Carmen Carmona-Garcia, Roser Fort-Culillas, Raquel Linan, Federica Zoratto, Gianpiero Rizzo, Marta Perachino, Kris Doonga, Gianluca Gaidano, Riccardo Bruna, Andrea Patriarca, Clara Martinez-Vila, Ignacio Perez Criado, Raffaele Giusti, Francesca Mazzoni, Lorenzo Antonuzzo, Armando Santoro, Alessandro Parisi, Paola Queirolo, Avinash Aujayeb, Lorenza Rimassa, Nikolaos Diamantis, Rossella Bertulli, Claudia A. M. Fulgenzi, Antonio D'Alessio, Isabel Ruiz-Camps, Nadia Saoudi-Gonzalez, David Garcia Illescas, Irene Medina, Laura Fox, Alessandra Gennari, Juan Aguilar-Company, David J. Pinato
Summary: This study aimed to investigate the long-term effects of previous immunization on evolving variants of SARS-CoV-2. The study found that patients who received the vaccine had fewer sequelae after COVID-19, as well as a lower incidence of respiratory complications and prolonged fatigue. This finding is important for the treatment and survival of cancer patients.
Article
Biochemistry & Molecular Biology
Mariona Terradas, Noemi Gonzalez-Abuin, Sandra Garcia-Mulero, Julen Viana-Errasti, Gemma Aiza, Josep M. Piulats, Joan Brunet, Gabriel Capella, Laura Valle
Summary: Germline mutations in MBD4 cause an autosomal recessive syndrome characterized by increased risk of acute myeloid leukemia, gastrointestinal polyposis, colorectal cancer, uveal melanoma, and schwannomas. However, a study of 728 patients with colorectal cancer, polyposis, and other suggestive phenotypes found that the identified heterozygous MBD4 variants were not associated with the disease.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Sara Fernandez-Castillejo, Barbara Roig, Mireia Mele, Sara Serrano, Monica Salvat, Montserrat Querol, Joan Brunet, Marta Pineda, Adela Cisneros, David Parada, Joan Badia, Joan Borras, Marta Rodriguez-Balada, Josep Guma
Summary: Multigene panel testing by next-generation sequencing can detect germline pathogenic or likely pathogenic variants in genes beyond those associated with a certain cancer phenotype. Opportunistic genetic screening based on this method can increase the diagnostic yield, facilitate the diagnosis of asymptomatic individuals, and provide an opportunity for early management of cancer.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Pathology
Julia Canet-Hermida, Fatima Marin, Eduard Dorca, Nuria Duenas, Laura Costas, Monica Salinas, Angela Velasco, Paula Peremiquel-Trillas, Sonia Paytubi, Jordi Ponce, Sergi Fernandez, Jose Manuel Martinez, Laura Cardenas, Anna Taltavull, Laia Alemany, Cristina Melendez, Gloria Oliveras, August Vidal, Gabriel Capella, Eugeni Lopez-Bonet, Joan Brunet, Xavier Matias-Guiu, Marta Pineda
Summary: The study explored the utility of highly sensitive MSI assessment in endometrial aspirates for individualized gynecologic surveillance in Lynch syndrome carriers. The results showed that hs-MSI assessment can detect cellular abnormalities in LS carriers in premalignant lesions, malignant lesions, and normal endometrium, and is associated with loss of mismatch repair proteins.
Article
Oncology
Ana Beatriz Sanchez-Heras, Teresa Ramon y Cajal, Marta Pineda, Elena Aguirre, Begona Grana, Isabel Chirivella, Judit Balmana, Joan Brunet
Summary: Li-Fraumeni syndrome is caused by TP53 gene heterozygous germline pathogenic variants. It is associated with a high risk of various malignant tumors in childhood and adulthood, including premenopausal breast cancer, soft tissue sarcomas and osteosarcomas, central nervous system tumors, and adrenocortical carcinomas. The concept of SLF has expanded to hereditable TP53-related cancer syndrome (hTP53rc) due to the variability of clinical manifestations, which don't always meet the classic criteria of Li-Fraumeni syndrome. Prospective studies are needed to assess genotype-phenotype characteristics and risk-adjusted recommendations.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2023)