Article
Oncology
Joseph D. Forrester, Deshka Foster, James M. Ford, Teri A. Longacre, Uri Ladabaum, Sara Fry, Jeffrey A. Norton
Summary: This study reports the long-term outcomes of total gastrectomy for patients with a family history of gastric cancer and CDH1 gene mutations that predispose to hereditary diffuse gastric cancer (HDGC). The results show that total gastrectomy is recommended for patients with inherited CDH1 mutations and the long-term quality of life following the surgery is acceptable.
Article
Oncology
Geoffrey Roberts, Patrick R. Benusiglio, Tanya Bisseling, Daniel Coit, Jeremy L. Davis, Sam Grimes, Theresa A. Guise, Richard Hardwick, Kirsty Harris, Paul Furman Mansfield, Jeremy Rossaak, Karen Chelcun Schreiber, Peter P. Stanich, Vivian E. Strong, Pardeep Kaurah
Summary: The study aims to define the standard of care for follow-up after prophylactic total gastrectomy (PTG) through a combination of literature review and two-round Delphi consensus. The guidelines provide a framework to best manage people following PTG, although the evidence supporting them is limited. They could also support the collection of information on the long-term effects of PTG.
Article
Oncology
Chihiro Matsumoto, Masaaki Iwatsuki, Shiro Iwagami, Takeshi Morinaga, Kohei Yamashita, Kenichi Nakamura, Kojiro Eto, Junji Kurashige, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Yoshihiro Komohara, Hideo Baba
Summary: A 41-year-old woman was admitted to the hospital for epigastralgia and was diagnosed with gastric adenocarcinoma with multiple liver metastases. Her genetic testing revealed a point mutation in the APC gene. Two older brothers and their mother also had the same genomic mutation and were diagnosed with GAPPS, undergoing prophylactic surgery.
Article
Gastroenterology & Hepatology
Hao Liu, Peng Jin, Xu Quan, Yi-Bin Xie, Fu-Hai Ma, Shuai Ma, Yang Li, Wen-Zhe Kang, Yan-Tao Tian
Summary: Evaluation of performing totally laparoscopic distal gastrectomy without prophylactic drains in selected patients showed that omitting prophylactic drainage may reduce surgery time and result in faster recovery. Routine prophylactic drains are not necessary in selected patients, but may be useful in high-risk patients.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Lidia-Sabina Cosma, Sophie Schlosser, Hauke C. Tews, Martina Mueller, Arne Kandulski
Summary: This article presents an overview of the genetic characteristics and current treatment approaches of hereditary diffuse gastric cancer (HDGC). It highlights the importance of the CTNNA1 gene, among others, in relation to this disease, and emphasizes the need for risk management in diagnosing patients through genetic testing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Bilal Asif, Amber Leila Sarvestani, Lauren A. Gamble, Sarah G. Samaranayake, Amber L. Famiglietti, Grace -Ann Fasaye, Martha Quezado, Markku Miettinen, Louis Korman, Christopher Koh, Theo Heller, Jeremy L. Davis
Summary: This study aimed to evaluate the safety and effectiveness of endoscopy in individuals with CDH1 variants, particularly in those who declined prophylactic total gastrectomy. The study found that endoscopy had a certain level of safety and effectiveness in early detection and interception of gastric cancer.
Article
Oncology
Mason D. Stillman, Nicole Kusche, Sabrina Toledano, Kimberly J. Hilfrank, Changhwan Yoon, Joel T. Gabre, Sheila D. Rustgi, Chin Hur, Fay Kastrinos, Sandra W. Ryeom, Sam S. Yoon
Summary: This study reviewed patients with CDH1 mutation who underwent PTG surgery and found that PTG can be performed safely at high-volume referral centers with good quality of life, although nutritional sequelae persist in some patients.
JOURNAL OF SURGICAL ONCOLOGY
(2022)
Article
Surgery
Javier Ithurralde-Argerich, Laura Rosner, Mariana Rizzolo, Alejandro Faerberg, Rolando Puma, Diego Ferro, Camilo Duque, Mirta Kujaruk, Federico Cuenca-Abente
Summary: Prophylactic total gastrectomy performed on patients with CDH1 mutations has shown high satisfaction rates and improved quality of life postoperatively. The procedure effectively prevents the development of advanced diffuse gastric cancer in these high-risk individuals.
JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES
(2021)
Article
Oncology
Zhiwen Pan, Zhixuan Fu, Cong Luo, Yejiang Bao, Mingli Wang, Wenming Cao, Xiaohong Xu
Summary: The frequency of CDH1 germline mutations in Chinese patients with HDGC is 7.4%, with new variants identified as N405Y and W409X. Among the 21 patients, up to 28.6% of CDH1 mutations were c.1775G>C (E551Q).
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Oncology
Paula Barauna de Assumpcao, Paulo Pimentel de Assumpcao, Fabiano Cordeiro Moreira, Andrea Ribeiro-Dos-Santos, Amanda F. Vidal, Leandro Magalhaes, Andre Salim Khayat, Andre Mauricio Ribeiro-dos-Santos, Giovanna C. Cavalcante, Adenilson Leao Pereira, Inacio Medeiros, Sandro Jose de Souza, Rommel Mario Rodriguez Burbano, Jorge Estefano Santana de Souza, Sidney Emanuel Batista Dos Santos
Summary: This study identifies new mutations associated with hereditary gastric cancer (HGC) and suggests that genetic ancestry may influence the identification of these mutations. Specifically, mutations were found in Amerindians and admixed populations with Amerindian genetic background, who suffer from early-onset gastric cancer. These newly reported mutations may contribute to early diagnosis and risk-reduction procedures for HGC.
Article
Oncology
Eiji Nomura
Summary: To improve the quality of surgical procedures for gastric cancer, various factors such as gastric motility, small intestinal absorption, hormones, and vagus nerve preservation need to be considered. Functional evaluation methods and patient position also play important roles. Preserving the three elements during gastrectomy, particularly the remnant stomach, is crucial for reconstruction methods and quality of life.
CHINESE JOURNAL OF CANCER RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Lyvianne Decourtye-Espiard, Parry Guilford
Summary: Hereditary diffuse gastric cancer (HDGC) is a dominantly inherited cancer syndrome characterized by a high incidence of diffuse gastric cancer (DGC) and lobular breast cancer (LBC). It is caused by germline mutations in the CDH1 and CTNNA1 genes. This article discusses the genetics, clinical phenotype, pathology, tumor initiation mechanism, natural history, and clinical management of HDGC.
Article
Surgery
Akihiro Sekimoto, Hideo Miyake, Hidemasa Nagai, Yuichiro Yoshioka, Norihiro Yuasa
Summary: This study aimed to investigate the risk factors for 1-year mortality after gastrectomy for gastric cancer and develop a scoring system for prediction. The results revealed that age, preoperative comorbidity, surgical procedure, postoperative complication, cancer stage, and surgical resection were important factors influencing 1-year survival. The scoring system could provide important information for surgeons to select the timing of advance care planning in patients with gastric cancer.
WORLD JOURNAL OF SURGERY
(2023)
Article
Oncology
Elio Adib, Talal El Zarif, Amin H. Nassar, Elie W. Akl, Sarah Abou Alaiwi, Tarek H. Mouhieddine, Edward D. Esplin, Kathryn Hatchell, Sarah M. Nielsen, Huma Q. Rana, Toni K. Choueiri, David J. Kwiatkowski, Guru Sonpavde
Summary: This study mapped the landscape of P/LP germline variants in the CDH1 gene across various cancers and ethnicities. The results showed significant enrichment of CDH1 P/LP variants in patients with CSRCC, DGC, and LBC across different ethnicities. Future prospective studies are needed to further validate these findings.
BRITISH JOURNAL OF CANCER
(2022)
Review
Oncology
Chen Nahshon, Yakir Segev, Ofer Gemer, Tomer Bar Noy, Meirav Schmidt, Ludmila Ostrovsky, Ofer Lavie
Summary: The study found that patients with BRCA1/2 mutations are at significantly higher risk for developing uterine cancer, especially uterine serous papillary cancer. This suggests that such cancers may be part of the BRCA1/2 syndrome. Therefore, the decision to perform concurrent hysterectomy during risk reduction bilateral salpingo-oophorectomy surgery should be considered on an individual basis.
GYNECOLOGIC ONCOLOGY
(2021)
Article
Genetics & Heredity
Ulrik Kristoffer Stoltze, Thomas Van Overeem Hansen, Jesper Sune Brok, Karen Gronskov, Asuman Z. Turner, Lise Barlebo Ahlborn, Kjeld Schmiegelow, Karin A. W. Wadt
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Oncology
Ulrik Kristoffer Stoltze, Jon Foss-Skiftesvik, Thomas van Overeem Hansen, Anna Byrjalsen, Astrid Sehested, David Scheie, Torben Stamm Mikkelsen, Simon Rasmussen, Mads Bak, Henrik Okkels, Michael Thude Callesen, Jane Skjoth-Rasmussen, Anne-Marie Gerdes, Kjeld Schmiegelow, Rene Mathiasen, Karin Wadt
Summary: This population-based study investigated the genetic predisposition of CNS tumors in children. Through whole-genome sequencing and pedigree analysis, the study found that approximately 10% of pediatric CNS tumors can be attributed to rare variants in known cancer genes. These genes associated with high risk of childhood cancer showed evolutionary evidence of constraint.
Article
Oncology
Denise G. O'Mahony, Susan J. Ramus, Melissa C. Southey, Nicola S. Meagher, Andreas Hadjisavvas, Esther M. John, Ute Hamann, Evgeny N. Imyanitov, Irene L. Andrulis, Priyanka Sharma, Mary B. Daly, Christopher R. Hake, Jeffrey N. Weitzel, Anna Jakubowska, Andrew K. Godwin, Adalgeir Arason, Anita Bane, Jacques Simard, Penny Soucy, Maria A. Caligo, Phuong L. Mai, Kathleen B. M. Claes, Manuel R. Teixeira, Wendy K. Chung, Conxi Lazaro, Peter J. Hulick, Amanda E. Toland, Inge Sokilde Pedersen, Susan L. Neuhausen, Ana Vega, Miguel de la Hoya, Heli Nevanlinna, Mallika Dhawan, Valentina Zampiga, Rita Danesi, Liliana Varesco, Viviana Gismondi, Valerio Gaetano Vellone, Paul A. James, Ramunas Janavicius, Liene Nikitina-Zake, Finn Cilius Nielsen, Thomas van Overeem Hansen, Tanja Pejovic, Ake Borg, Johanna Rantala, Kenneth Offit, Marco Montagna, Katherine L. Nathanson, Susan M. Domchek, Ana Osorio, Maria J. Garcia, Beth Y. Karlan, Anna De Fazio, David Bowtell, Lesley McGuffog, Goska Leslie, Michael T. Parsons, Thilo Doerk, Lisa-Marie Speith, Elizabeth Santana dos Santos, Alexandre Andre B. A. da Costa, Paolo Radice, Paolo Peterlongo, Laura Papi, Christoph Engel, Eric Hahnen, Rita K. Schmutzler, Barbara Wappenschmidt, Douglas F. Easton, Marc Tischkowitz, Christian F. Singer, Yen Yen Tan, Alice S. Whittemore, Weiva Sieh, James D. Brenton, Drakoulis Yannoukakos, Florentia Fostira, Irene Konstantopoulou, Jana Soukupova, Michal Vocka, Georgia Chenevix-Trench, Paul D. P. Pharoah, Antonis C. Antoniou, David E. Goldgar, Amanda B. Spurdle, Kyriaki Michailidou, Marian J. E. Mourits, Fabienne Lesueur
Summary: This study assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity and provided evidence for improved classification and clinical management of carriers.
BRITISH JOURNAL OF CANCER
(2023)
Article
Genetics & Heredity
Anne Marie Jelsig, Thomas van Overeem Hansen, Lene Bjerring Gede, Niels Qvist, Lise-Lotte Christensen, Charlotte Kvist Lautrup, Jane Huebertz Frederiksen, Lone Sunde, Lilian Bomme Ousager, Ken Ljungmann, Birgitte Bertelsen, John Gasdal Karstensen
Summary: Peutz-Jeghers syndrome (PJS) is a hereditary polyposis syndrome with a high risk of cancer and death. In this study, the genetic etiology of all known PJS patients in Denmark was identified, and the risks of cancer, surveillance effects, and overall survival were estimated. Most cases of cancer were found between scheduled examinations, highlighting the need for improved clinical care.
Article
Oncology
Anne Marie Jelsig, Thomas van Overeem Hansen, Lene Bjerring Gede, Niels Qvist, Lise-Lotte Christensen, Charlotte Kvist Lautrup, Ken Ljungmann, Louise Torp Christensen, Karina Ronlund, Pernille Mathiesen Torring, Birgitte Bertelsen, Lone Sunde, John Gasdal Karstensen
Summary: Juvenile polyposis syndrome (JPS) is a hereditary syndrome characterized by gastrointestinal juvenile polyps and increased risk of gastrointestinal cancer. Genetic analysis was performed on Danish patients with a clinical diagnosis of JPS or pathogenic variants in BMPR1A or SMAD4. The study revealed that the majority of JPS patients have pathogenic variants in BMPR1A, SMAD4, or PTEN, and not all patients with a pathogenic variant fulfill the clinical criteria of JPS. The study also demonstrated a wide clinical spectrum and variability in the histopathology of removed polyps.
Article
Genetics & Heredity
Anne Marie Jelsig, Karina Ronlund, Lene Bjerring Gede, Jane Huebertz Frederiksen, John Gasdal Karstensen, Ulf Birkedal, Thomas van Overeem Hansen
Summary: A 59-year-old male with colorectal juvenile polyps was diagnosed with PTEN-hamartoma tumour syndrome through genetic analysis and whole genome sequencing. A novel intronic variant of unknown significance in PTEN was detected, leading to a pseudoexon inclusion that introduced a frameshift and a premature stop codon. This is the first report of a variant resulting in pseudoexon inclusion in PTEN.
JOURNAL OF HUMAN GENETICS
(2023)
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
Ulrik Kristoffer Stoltze, Mathis Hildonen, Thomas Van Overeem Hansen, Jon Foss-Skiftesvik, Anna Byrjalsen, Malene Lundsgaard, Laura Pignata, Karen Gronskov, Asuman Z. Tumer, Kjeld Schmiegelow, Jesper Sune Brok, Karin A. W. Wadt
Summary: This study found that the development of Wilms tumors is associated with genetic and epigenetic factors, with female patients more likely to carry pathogenic variants. Early detection of underlying predisposition may have important implications for diagnosis, treatment, and genetic counseling for Wilms tumors.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
Ulrik Kristoffer Stoltze, Christian Munch Hagen, Thomas van Overeem Hansen, Anna Byrjalsen, Anne-Marie Gerdes, Victor Yakimov, Simon Rasmussen, Marie Baekvad-Hansen, David Michael Hougaard, Kjeld Schmiegelow, Henrik Hjalgrim, Karin Wadt, Jonas Bybjerg-Grauholm
Summary: A new method called double batched sequencing has been developed to lower the cost of genetic testing while maintaining diagnostic power. By sequencing blood spot samples collected at birth, cancer-causing germline variants can be detected. The method is highly scalable and significantly reduces the cost of screening for rare disease-causing mutations.
Letter
Neurosciences
Jon Foss-Skiftesvik, Rene Mathiasen, Thomas van Overeem Hansen, Karin Wadt, Kjeld Schmiegelow, Ulrik Kristoffer Stoltze
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Maria Bejerholm Boelman, Thomas van Overeem Hansen, Matthias Nybro Smith, Sophia Hammer-Hansen, Alex Horby Christensen, Birgitte Rode Diness
Summary: Pathogenic variants in genes involved in smooth muscle function or regulation can increase the risk of congenital heart disease and thoracic aortic aneurysm and dissection. This case report presents a patient with persistent ductus arteriosus and thoracic aortic dissection, with a novel splice acceptor variant in the MYLK gene identified as the genetic cause.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Clinical Neurology
Maria Barington, Morten Duno, Ulf Birkedal, John Vissing, Alfred Peter Born, Thomas Krag, Elsebet ostergaard
Summary: The three major collagen VI genes (COL6A1, COL6A2, and COL6A3) encode microfibrillar components of the extracellular matrix in various tissues. A pathogenic variant (c.1741-6G > A) in the COL6A1 gene was identified in three patients with severe Ullrich congenital muscular dystrophy. The variant induces aberrant splicing, leading to loss of collagen VI function and impaired secretion. This finding expands our understanding of pathogenic variants causing Ullrich congenital muscular dystrophy.
NEUROMUSCULAR DISORDERS
(2023)
Article
Obstetrics & Gynecology
Jesper Friis Petersen, Lennart Jan Friis-Hansen, Thue Bryndorf, Andreas Kryger Jensen, Anders Nyboe Andersen, Ellen Lokkegaard
Summary: This study aimed to develop a dynamic model using baseline demographic data and collected blood samples and transvaginal sonographies to predict the outcome of pregnancy during the first trimester. The study found that over 1/5 of the women had a higher risk of miscarriage, and detecting fetal heart rate before 8 weeks' gestation had a 90% chance of subsequent delivery. Factors such as maternal age, crown-rump length (CRL), bleeding, and serum biomarkers like hCG, progesterone, and estradiol impacted the risk of miscarriage.
REPRODUCTIVE SCIENCES
(2023)
Article
Medical Laboratory Technology
Sofie Lieberoth, Frederik Friis-Hansen, Lennart Friis-Hansen
Summary: This study measured plasma chromogranin A (CgA) concentrations in different age groups of healthy children and adolescents. The results showed that plasma CgA concentrations decrease with age. The reference intervals obtained in this study will be useful for screening, diagnosing, and monitoring neuroendocrine neoplasms (NENs) in children.
ANNALS OF CLINICAL BIOCHEMISTRY
(2023)
Article
Genetics & Heredity
Anna Byrjalsen, Ulrik Stoltze, Mana Mehrjouy, Jane Hubertz Frederiksen, Mads Bak, Ulf Birkedal, Henrik Hasle, Anne-Marie Gerdes, Kjeld Schmiegelow, Karin Wadt, Thomas van Overeem Hansen
Summary: This study reports a new SMARCA4 deletion in a female patient with ovarian small cell carcinoma and hypercalcemia. The deletion was found to have different effects on the RNA level, highlighting the importance of incorporating RNA analysis in the classification of single-exon deletions.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)