Article
Genetics & Heredity
Adelyn Beil, Whitney Hornsby, Wendy R. Uhlmann, Rajani Aatre, Patricia Arscott, Brooke Wolford, Kim A. Eagle, Bo Yang, Jennifer McNamara, Cristen Willer, J. Scott Roberts
Summary: Disclosure of pathogenic variants to thoracic aortic dissection biobank participants was carried out, with participants satisfied with the process. The impact on participants' psychosocial well-being was found to be low, and while the process required significant time and resources, the return of clinically significant results and CLIA laboratory testing was positively received.
BMC MEDICAL GENOMICS
(2021)
Review
Genetics & Heredity
Austin A. Saugstad, Natasha Petry, Catherine Hajek
Summary: As our understanding of genomics and genetic testing continues to advance, the personalization of medical decision making is progressing simultaneously. By carefully crafting medical care to fit the specific needs of the individual, patients can experience better long-term outcomes, reduced toxicities, and improved healthcare experiences. Studies have revealed diverse relationships between specific genetic variants and available therapies, ranging from well-documented clinical approaches to potential future applications.
FRONTIERS IN GENETICS
(2022)
Review
Clinical Neurology
Juliet K. Knowles, Ingo Helbig, Cameron S. Metcalf, Laura S. Lubbers, Lori L. Isom, Scott Demarest, Ethan M. Goldberg, Alfred L. George, Holger Lerche, Sarah Weckhuysen, Vicky Whittemore, Samuel F. Berkovic, Daniel H. Lowenstein
Summary: The genetic basis of epilepsy is becoming better understood, opening up the possibility for precision treatments based on specific genetic causes. However, current medical therapy for epilepsy is still imprecise and mainly focused on reducing seizures empirically. Despite significant advancements in diagnosis and technology, there has been limited impact on clinical practice. Nevertheless, the epilepsy community is poised to make significant progress in precision therapy through continued innovations in gene discovery, diagnostics, and bioinformatics, increased accessibility to genetic testing, and a greater understanding of the natural course of the disease.
Article
Biochemistry & Molecular Biology
Fabio Pastorino, Mario Capasso, Chiara Brignole, Serena Giglio, Veronica Bensa, Sueva Cantalupo, Vito Alessandro Lasorsa, Annalisa Tondo, Rossella Mura, Angela Rita Sementa, Alberto Garaventa, Mirco Ponzoni, Loredana Amoroso
Summary: Neuroblastoma is the most common extracranial solid tumor in childhood. The prognosis for patients with metastatic relapse or refractory disease is poor. The integration of genome sequencing into standard clinical practice is necessary for personalized therapy. In this study, whole exome sequencing was performed on two patients with relapsed NB, and actionable genetic variations were identified and treated accordingly. The results demonstrate the feasibility of incorporating clinical WES into pediatric oncology practice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Matt A. Field
Summary: Precision medicine programs have been revolutionized by affordable high-throughput sequencing technologies, enabling the identification of clinically relevant genetic variation. However, the timely analysis and interpretation of variant information remain challenging, and larger bioinformatic challenges may arise in the future. Novel statistical models and software are needed to fully realize the potential of precision medicine programs.
FRONTIERS IN MEDICINE
(2022)
Article
Oncology
Jai N. Patel, Danielle Boselli, Elizabeth J. Jandrisevits, Issam S. Hamadeh, Ahmed Salem, Patrick Meadors, Declan Walsh
Summary: Approximately half of the patients received at least one symptom control medication, with the majority receiving SCMs with pharmacogenetic evidence. The study found a significant correlation between symptom severity and SCM prescribing.
SUPPORTIVE CARE IN CANCER
(2021)
Article
Genetics & Heredity
Megan T. Lynch, Kristin A. Maloney, Toni I. Pollin, Elizabeth A. Streeten, Huichun Xu, Alan R. Shuldiner, Cristopher V. Van Hout, Claudia Gonzaga-Jauregui, Braxton D. Mitchell
Summary: Founder populations like the Lancaster Amish exhibit higher frequencies of specific pathogenic genetic variants compared to nonfounder populations, offering opportunities for more efficient precision medicine interventions.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Genetics & Heredity
Turki M. Sobahy, Ghassan Tashkandi, Donya Bahussain, Raneem Al-Harbi
Summary: The recent development of parallel sequencing technology in oncology has generated a large amount of cell-specific genetic information, but the interpretation and classification of these variants remain challenging and lack standardization. The AMP, ASCO, and CAP have released consensus guidelines for the cataloging and clinical annotations of cell-specific variants. A new computational method was developed and applied to tumor-specific databases to produce a clinically actionable cancer somatic variants dataset. The study also highlighted the challenges and limitations of using different classification systems or computational methods.
BMC MEDICAL GENOMICS
(2022)
Article
Multidisciplinary Sciences
Federica Luppino, Ivan A. Adzhubei, Christopher A. Cassa, Agnes Toth-Petroczy
Summary: The authors develop a supervised variant effect predictor for use in clinically actionable genes using evolutionary and structural relationships between residues. This tool improves performance over existing predictors by reaching balanced specificity and sensitivity on clinical data, and includes a novel feature called the 'partners score' to model epistatic interactions. The predictions for missense variants in 316 clinically actionable disease genes are available on demag.org.
NATURE COMMUNICATIONS
(2023)
Article
Public, Environmental & Occupational Health
Niccolo Tempini, Sabina Leonelli
Summary: This paper examines the actionability and trust of genomic data in medical research, discussing the case of COSMIC as a leading cancer genomics database and comparing exploratory and diagnostics research. Researchers highlight various questions and concerns when using genomic data in different situations, while also acknowledging similarities in evaluation and re-use strategies.
SOCIAL SCIENCE & MEDICINE
(2021)
Article
Oncology
Pushpinder Kaur, Tania B. Porras, Anthony Colombo, Alexander Ring, Janice Lu, Irene Kang, Julie E. Lang
Summary: The study found that over 30% of tumors carried potentially actionable events targetable by existing drugs, identified genes with multiple targetable alterations as candidates for combination therapy, and drivers in primary breast tumors fall into five categories. Analysis showed that copy number alterations and mutations in genes were significantly associated with gene expression, validating copy number events as a dominant oncogenic mechanism in breast cancer.
BRITISH JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Aldo Spanjaard, Ronak Shah, Daniel de Groot, Olimpia Alessandra Buoninfante, Ben Morris, Cor Lieftink, Colin Pritchard, Lisa M. Zurcher, Shirley Ormel, Joyce J. Catsman, Renske De Korte-Grimmerink, Bjorn Siteur, Natalie Proost, Terry Boadum, Marieke van de Ven, Ji-Ying Song, Maaike Kreft, Paul C. M. van den Berk, Roderick L. Beijersbergen, Heinz Jacobs
Summary: PCNA-ubiquitination and REV1 play distinct roles in DNA damage tolerance, particularly in tolerating cisplatin lesions. Polymerase Kappa is essential in tolerating multiple genotoxic lesions, including cisplatin lesions.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Elisa De Paolis, Ida Paris, Bruno Tilocca, Paola Roncada, Laura Foca, Giordana Tiberi, Tatiana D'Angelo, Francesco Pavese, Margherita Muratore, Luisa Carbognin, Giorgia Garganese, Riccardo Masetti, Alba Di Leone, Alessandra Fabi, Giovanni Scambia, Andrea Urbani, Daniele Generali, Angelo Minucci, Concetta Santonocito
Summary: Breast cancer is the leading cause of cancer-related death in women worldwide, with BRCA1 and BRCA2 genes accounting for a significant portion of hereditary breast cancer. Classifying variants accurately is important for risk-reducing surgeries, treatment planning, and familial surveillance.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Karin P. S. Langenberg, Eleonora J. Looze, Jan J. Molenaar
Summary: Precision medicine is a revolutionary approach to cancer treatment that targets specific genetic changes in individual patients to improve cure rates and reduce toxicity. The characteristics and early results of precision medicine programs in pediatric oncology show potential clinical benefits. Future perspectives include incorporating novel approaches and collaborative trial designs to target aberrations in childhood malignancies.
Review
Pharmacology & Pharmacy
George T. Chen, Daniel H. Geschwind
Summary: Neurodevelopmental Disorders (NDDs) encompass a wide range of disorders, including autism spectrum disorders (ASD) and schizophrenia (SCZ), which are linked to brain developmental processes. The clinical treatment of these disorders has traditionally focused on symptom management due to the variability in developmental disruption and limited knowledge of the underlying molecular mechanisms. With the identification of several hundred genes associated with ASD and SCZ, there is potential for new therapeutic approaches and the opportunity for precision medicine. This review discusses the progress in research technologies that enhance our understanding of disease progression and highlights advances in targeted clinical treatment and ongoing preclinical efforts in NDD precision medicine.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
