Article
Oncology
Yoo-Na Kim, Min Kyu Kim, Young Joo Lee, Youngeun Lee, Ji Yeon Sohn, Jung-Yun Lee, Min Chul Choi, Migang Kim, Sang Geun Jung, Won Duk Joo, Chan Lee
Summary: This study investigated the prevalence and relative contributions of Lynch Syndrome (LS) and non-LS mutations in Korean patients with endometrial cancer. By analyzing the medical records of 204 patients, it was found that 13% of patients had LS, and patients with LS were more likely to be younger at diagnosis and meet the Amsterdam II criteria. The study also identified a higher prevalence of non-endometrioid histology in patients with MSH6 or PMS2 mutations.
Article
Oncology
Ramadhani Chambuso, Barbara Robertson, Raj Ramesar
Summary: Lynch syndrome is a common cancer predisposition disease, characterized by colorectal cancer. It is important to identify the germline pathogenic variants causing Lynch syndrome for effective cascade screening. However, performing next generation sequencing on the entire cohort of colorectal cancer patients, even in limited age groups, is a burden on limited resources.
Article
Multidisciplinary Sciences
Yunbeom Lee, Ji Ae Lee, Hye Eun Park, Hyojun Han, Yuhnam Kim, Jeong Mo Bae, Jung Ho Kim, Nam-Yun Cho, Hwang-Phill Kim, Tae-You Kim, Gyeong Hoon Kang
Summary: A new computational method and microsatellite marker panels were developed to assess and detect microsatellite instability in CRC, which does not require paired normal tissues. It showed good sensitivity and specificity for different types of samples.
Article
Genetics & Heredity
Wu Jiang, Lin Li, Chuan-Feng Ke, Wei Wang, Bin-Yi Xiao, Ling-Heng Kong, Jing-Hua Tang, Yuan Li, Xiao-Dan Wu, Ying Hu, Wei-Hua Guo, Si-Zhen Wang, De-Sen Wan, Rui-Hua Xu, Zhi-Zhong Pan, Pei-Rong Ding
Summary: This study found that universal germline testing in patients with colorectal cancer can help identify potential hereditary cancer syndromes, especially in those under 70 years old. Enhanced surveillance and tailored treatment may be beneficial for patients with germline pathogenic variants.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Gastroenterology & Hepatology
Si-Yu He, Ying-Chun Li, Yong Wang, Hai-Lin Peng, Cheng-Lin Zhou, Chuan-Meng Zhang, Sheng-Lan Chen, Jian-Feng Yin, Mei Lin
Summary: This study used NGS to sequence stool DNA from CRC patients, screened specific genes or gene combinations suitable for diagnosis and prognostic prediction of CRC, and comprehensively evaluated their significance in diagnosing CRC and predicting patients' prognosis. The results of the study showed that TP53 and KRAS genes can be used for CRC screening, diagnosis, and prognostic prediction, and combined testing can improve the detection rate of CRC. Furthermore, new mutation sites were found that require further research to determine their clinical significance.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Oncology
Federico Pio Fabrizio, Stefano Castellana, Flavia Centra, Angelo Sparaneo, Mario Mastroianno, Tommaso Mazza, Michelina Coco, Domenico Trombetta, Nicola Cingolani, Antonella Centonza, Paolo Graziano, Evaristo Maiello, Vito Michele Fazio, Lucia Anna Muscarella
Summary: DNA methylation is a significant epigenetic mark in cancer cells, and methylation profiles have been suggested as promising biomarkers for cancer. Researchers designed and validated a novel targeted NGS panel for methylation analysis, which can evaluate methylation levels of multiple cancer-related genes simultaneously.
FRONTIERS IN ONCOLOGY
(2022)
Article
Genetics & Heredity
Pham Nguyen Quy, Keita Fukuyama, Masashi Kanai, Tadayuki Kou, Tomohiro Kondo, Masahiro Yoshioka, Junichi Matsubara, Tomohiro Sakuma, Sachiko Minamiguchi, Shigemi Matsumoto, Manabu Muto
Summary: Tumor heterogeneity can cause inter-assay discordance in next-generation sequencing results. The concordance between two different assays can also be affected by sample types and the analytical features of each panel.
BMC MEDICAL GENOMICS
(2022)
Article
Biology
Maria Guarnaccia, Laura Guarnaccia, Valentina La Cognata, Stefania Elena Navone, Rolando Campanella, Antonella Ampollini, Marco Locatelli, Monica Miozzo, Giovanni Marfia, Sebastiano Cavallaro
Summary: The study developed a targeted next-generation sequencing approach for analyzing genetic variations and chromosomal aberrations in gliomas, which can provide accurate and specific assessment of tumor pathogenesis, prognosis, and treatment response. This has important implications for the diagnosis and treatment of gliomas.
Article
Medicine, Research & Experimental
Jing Wang, Ruiyu Li, Junjie Li, Yuting Yi, Xiaoding Liu, Jingci Chen, Hui Zhang, Junliang Lu, Cami Li, Huanwen Wu, Zhiyong Liang
Summary: This study utilized DNA and RNA sequencing to detect fusion genes in dMMR CRCs, revealing that fusion-positive tumors tend to occur in older patients, are predominantly right-sided, and display mutations in key WNT pathway components.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Soyoun Rachel Kim, Leslie Oldfield, Alicia Tone, Aaron Pollett, Stephanie Pedersen, Johanna Wellum, Matthew Cesari, Katherine Lajkosz, Trevor J. Pugh, Sarah Elizabeth Ferguson
Summary: Abnormalities in mismatch repair have been studied in ovarian cancer, but this study focuses on the causes of mismatch repair deficiency (MMRd). The research found that Lynch syndrome is a major cause of MMRd in ovarian cancer, and a custom next generation sequencing panel was used to assess both hereditary and somatic causes of MMRd in ovarian cancer.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2023)
Article
Genetics & Heredity
Jing Ma, Xiuli Ma, Ken Lin, Rui Huang, Xianyun Bi, Cheng Ming, Li Li, Xia Li, Guo Li, Liping Zhao, Tao Yang, Yingqin Gao, Tiesong Zhang
Summary: This study conducted genetic sequencing analysis on 879 deaf Chinese children in Yunnan, and identified 428 deafness gene variants, with GJB2 and SLC26A4 being the most common genes. The study also found that the genetic characteristics of deafness in this region differ from other regions and ethnic groups, suggesting the need for customized genetic screening programs.
Article
Multidisciplinary Sciences
Keitaro Shimozaki, Hideyuki Hayashi, Shigeki Tanishima, Sara Horie, Akihiko Chida, Kai Tsugaru, Kazuhiro Togasaki, Kenta Kawasaki, Eriko Aimono, Kenro Hirata, Hiroshi Nishihara, Takanori Kanai, Yasuo Hamamoto
Summary: The study found that NGS and PCR methods showed good concordance in the positive and negative predictive values for detecting MSI-H/dMMR, with NGS also demonstrating potential applications in clinical practice.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Ayushi Jain, Maryam Alimirah, Heather Hampel, Rachel Pearlman, Jianing Ma, Jing Peng, Matthew F. Kalady, Peter P. Stanich
Summary: Multiple colorectal adenomas (MCRA) are not uncommon in Lynch syndrome and are associated with a significantly increased likelihood of advanced colon neoplasia.
FRONTIERS IN ONCOLOGY
(2022)
Article
Genetics & Heredity
Jaymi Tan, Yock Ping Chow, Norziha Zainul Abidin, Kian Meng Chang, Veena Selvaratnam, Nor Rafeah Tumian, Yang Ming Poh, Abhi Veerakumarasivam, Michael Arthur Laffan, Chieh Lee Wong
Summary: This study validated the technical performance of a custom 22-gene NGS panel and used it to screen 10 clinical MPN samples. The NGS analysis showed high accuracy and identified known and novel variants, supporting its potential clinical utility in the management of MPNs.
BMC MEDICAL GENOMICS
(2022)
Article
Medicine, General & Internal
Gabriele Bonetti, Kristjana Dhuli, Maria Rachele Ceccarini, Jurgen Kaftalli, Michele Samaja, Vincenza Precone, Stefano Cecchin, Paolo Enrico Maltese, Giulia Guerri, Giuseppe Marceddu, Tommaso Beccari, Barbara Aquilanti, Valeria Velluti, Giuseppina Matera, Marco Perrone, Amerigo Iaconelli, Francesca Colombo, Francesco Greco, Marco Raffaelli, Mahmut Cerkez Ergoren, Matteo Bertelli
Summary: Obesity is a chronic disease that poses health risks and leads to other chronic illnesses, with 19.8% of the adult population in Italy being obese. A study has found that using a next-generation sequencing (NGS) gene panel can help evaluate an individual's predisposition to obesity and their response to bariatric surgery, potentially predicting the surgical outcome.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Public, Environmental & Occupational Health
Sukh Makhnoon, Deborah J. Bowen, Brian H. Shirts, Stephanie M. Fullerton, Hendrika W. Meischke, Eric B. Larson, James D. Ralston, Kathleen Leppig, David R. Crosslin, David Veenstra, Gail P. Jarvik
Summary: This study found that patients' genetic knowledge was associated with their future intended familial communication of genetic information, but not with current communication of colorectal cancer risk. Better family functioning was associated with more frequent current communication of CRC risk.
TRANSLATIONAL BEHAVIORAL MEDICINE
(2021)
Article
Public, Environmental & Occupational Health
Deborah J. Bowen, Sukh Makhnoon, Brian H. Shirts, Stephanie M. Fullerton, Eric Larson, James D. Ralston, Kathleen Leppig, David R. Crosslin, David Veenstra, Gail P. Jarvik
Summary: The study found infrequent communication of cancer risk among family members, with a low overall impact of communication within the family. Age and education were associated with the frequency of familial communication, but not with the cancer-related impact of familial communication.
PATIENT EDUCATION AND COUNSELING
(2021)
Article
Genetics & Heredity
Stephen E. Lincoln, Tina Hambuch, Justin M. Zook, Sara L. Bristow, Kathryn Hatchell, Rebecca Truty, Michael Kennemer, Brian H. Shirts, Andrew Fellowes, Shimul Chowdhury, Eric W. Klee, Shazia Mahamdallie, Megan H. Cleveland, Peter M. Vallone, Yan Ding, Sheila Seal, Wasanthi DeSilva, Farol L. Tomson, Catherine Huang, Russell K. Garlick, Nazneen Rahman, Marc Salit, Stephen F. Kingsmore, Matthew J. Ferber, Swaroop Aradhya, Robert L. Nussbaum
Summary: The study evaluated the impact of technically challenging variants on clinical genetic tests, finding considerable variability in the analytic and clinical sensitivity of NGS workflows. Some challenging variants were not detected by all workflows, highlighting the importance of test design, validation, and selection for clinicians.
GENETICS IN MEDICINE
(2021)
Article
Allergy
Sarah K. Baxter, Tom Walsh, Silvia Casadei, Mary M. Eckert, Eric J. Allenspach, David Hagin, Gesmar Segundo, Ming K. Lee, Suleyman Gulsuner, Brian H. Shirts, Kathleen E. Sullivan, Michael D. Keller, Troy R. Torgerson, Mary-Claire King
Summary: This study identified damaging germline mutations in 27 genes in about 39% of patients with childhood-onset immune dysregulation, polyendocrinopathy, and enteropathy. Many of these genes had not been previously associated with the disease. Genetic diagnoses of these patients have clinical implications and can potentially alter therapeutic management, providing targeted treatments and recommendations for hematopoietic cell transplantation.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Medical Informatics
Luke V. Rasmussen, John J. Connolly, Guilherme Del Fiol, Robert R. Freimuth, Douglas B. Pet, Josh F. Peterson, Brian H. Shirts, Justin B. Starren, Marc S. Williams, Nephi Walton, Casey Overby Taylor
Summary: This study aimed to understand potential barriers to the adoption of health information technology projects released as free and open source software. Through a survey and analysis of research consortia participants, 14 categories of perceived barriers were identified, with recommendations for addressing them. FOSS developers need to ensure their systems are easy to trial and implement, and institutional champions will remain critical for prioritizing genomic medicine projects.
APPLIED CLINICAL INFORMATICS
(2021)
Article
Genetics & Heredity
Anja R. Ollodart, Chiann-Ling C. Yeh, Aaron W. Miller, Brian H. Shirts, Adam S. Gordon, Maitreya J. Dunham
Summary: This study established a new method to simultaneously determine the mutation rate of multiple strains using continuous culture devices and deep sequencing, successfully applied to assay the mutation rate of Saccharomyces cerevisiae strains with mutations in the Msh2 gene. The method was proven to be accurate and reliable, and it can be applied to studying the mutation rate of various microbial species.
Article
Genetics & Heredity
Shawn Fayer, Carrie Horton, Jennifer N. Dines, Alan F. Rubin, Marcy E. Richardson, Kelly McGoldrick, Felicia Hernandez, Tina Pesaran, Rachid Karam, Brian H. Shirts, Douglas M. Fowler, Lea M. Starita
Summary: The combination of multiplexed functional data with clinical data can effectively drive the reclassification of missense variants, reducing the number of variants of uncertain significance and having a major impact on clinical variant interpretation.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Urology & Nephrology
Kara N. Maxwell, Heather H. Cheng, Jacquelyn Powers, Roman Gulati, Elisa M. Ledet, Casey Morrison, Anh Le, Ryan Hausler, Jill Stopfer, Sophie Hyman, Wendy Kohlmann, Anne Naumer, Jennie Vagher, Samantha E. Greenberg, Lorraine Naylor, Mercy Laurino, Eric Q. Konnick, Brian H. Shirts, Saud H. AlDubayan, Eliezer M. Van Allen, Bastien Nguyen, Joseph Vijai, Wassim Abida, Maria Carlo, Marianne Dubard-Gault, Daniel J. Lee, Luke D. Maese, Diana Mandelker, Bruce Montgomery, Michael J. Morris, Piper Nicolosi, Robert L. Nussbaum, Lauren E. Schwartz, Zsofia Stadler, Judy E. Garber, Kenneth Offit, Joshua D. Schiffman, Peter S. Nelson, Oliver Sartor, Michael F. Walsh, Colin C. Pritchard
Summary: Complementary analysis of prostate cancer incidence in LFS males and gTP53 prevalence in prostate cancer cohorts suggests that gTP53 predisposes to aggressive prostate cancer. Prostate cancer should be considered as part of LFS screening protocols and TP53 should be considered in germline prostate cancer susceptibility testing.
Article
Genetics & Heredity
Steven M. Harrison, Christina A. Austin-Tse, Serra Kim, Matthew Lebo, Annette Leon, David Murdock, Aparna Radhakrishnan, Brian H. Shirts, Marcie Steeves, Eric Venner, Richard A. Gibbs, Gail P. Jarvik, Heidi L. Rehm
Summary: The All of Us Research Program aims to accelerate research and improve healthcare by collecting data from one million people in the United States. Participants can choose to receive genome analysis results, including actionable findings for certain gene-disorder pairs. Four participating clinical laboratories conducted a prelaunch study to ensure consistent reporting of variant classifications, with 99.1% concordance and resolution of all reportability differences through reassessment and discussion. This approach will be maintained for continuous classification harmonization and consistent reporting within the program.
Article
Genetics & Heredity
Laura M. Amendola, Elizabeth Shuster, Michael C. Leo, Michael O. Dorschner, Bradley A. Rolf, Brian H. Shirts, Marian J. Gilmore, Sonia Okuyama, Jamilyn M. Zepp, Tia L. Kauffman, Kathleen F. Mittendorf, Cecilia Bellcross, Charisma L. Jenkins, Galen Joseph, Leslie Riddle, Sapna Syngal, Chinedu Ukaegbu, Katrina A. B. Goddard, Benjamin S. Wilfond, Gail P. Jarvik
Summary: This study aims to evaluate the laboratory-related outcomes of participants offered genomic testing based on cancer family history risk assessment tools. The study found that 5% of participants had a pathogenic/likely pathogenic cancer risk variant and 1% had a secondary finding. Participant personal history and PREMM5 score were associated with the category of findings.
GENETICS IN MEDICINE
(2022)
Article
Genetics & Heredity
Ronald W. Buie, John Michael O. Ranola, Annie T. Chen, Brian H. Shirts
Summary: This paper proposes an algorithm to evaluate the variant information gain in familial cosegregation analysis, and validates its performance by comparing actual recruitment strategies with optimized testing strategies. The results show that the testing strategy indicated by the algorithm can achieve maximal information gain more rapidly.
Article
Genetics & Heredity
Shangqing Jiang, Patrick C. Mathias, Nathaniel Hendrix, Brian H. Shirts, Peter Tarczy-Hornoch, David Veenstra, Daniel Malone, Beth Devine
Summary: A cost-effectiveness model was constructed to evaluate the clinical and economic value of a CDS alert program providing PGx testing results in ACS and AF. The program was found to significantly reduce major clinical events and deaths in ACS and AF, and was cost-effective with an incremental cost-effectiveness ratio of $39,477/QALY compared to no alert program, under a willingness-to-pay threshold of $100,000/QALY gained.
PHARMACOGENOMICS JOURNAL
(2022)
Article
Health Care Sciences & Services
E. J. Dusic, Deborah J. Bowen, Robin Bennett, Kevin C. Cain, Tesla Theoryn, Mariebeth Velasquez, Elizabeth Swisher, Jeannine M. Brant, Brian Shirts, Catharine Wang
Summary: This study found that socioeconomic status affects individuals' interest in pursuing hereditary cancer genetic testing, with factors such as education and household income being related to the level of interest.
Article
Medicine, Research & Experimental
Wei-Liang Chen, Emily Pao, James Owens, Ian Glass, Colin Pritchard, Brain H. Shirts, Christina Lockwood, Ghayda M. Mirzaa
Summary: The megalencephaly-capillary malformation (MCAP) syndrome is an overgrowth disorder caused by mosaic gain-of-function variants in PIK3CA. This study reports the utility of cerebrospinal fluid (CSF)-derived cfDNA for the molecular diagnosis of MCAP syndrome and highlights the importance of minimally invasive approaches using cfDNA for accurate diagnosis and potential therapeutic implications for individuals with refractory epilepsy.
COLD SPRING HARBOR MOLECULAR CASE STUDIES
(2022)
Article
Oncology
Rachel Pearlman, Wendy L. Frankel, Benjamin J. Swanson, Dan Jones, Weiqiang Zhao, Ahmet Yilmaz, Kristin Miller, Jason Bacher, Christopher Bigley, Lori Nelsen, Paul J. Goodfellow, Richard M. Goldberg, Electra Paskett, Peter G. Shields, Jo L. Freudenheim, Peter P. Stanich, Ilene Lattimer, Mark Arnold, Thomas W. Prior, Mitchell Haut, Matthew F. Kalady, Brandie Heald, Ian Paquette, David J. Draper, Joanna M. Brell, Sameer Mahesh, Kisa Weeman, Shyamal Bastola, Jeffrey Zangmeister, Aruna Gowda, Filix Kencana, Albert Malcolm, Yinong Liu, Sharon Cole, Charles Bane, Chaoyang Li, Esther Rehmus, Colin C. Pritchard, Brian H. Shirts, Angela Jacobson, Shelly A. Cummings, Albert de la Chapelle, Heather Hampel
Summary: The study found that 7.1% of individuals with CRC have PGVs, and UTS alone is insufficient for identifying a large proportion of CRC patients with hereditary syndromes, including some with LS. Pan-cancer MGPT for all patients with CRC may be a better screening method.
JCO PRECISION ONCOLOGY
(2021)