Article
Oncology
Lizhen Zhu, Beiping Miao, Dagmara Dymerska, Magdalena Kuswik, Elena Bueno-Martinez, Lara Sanoguera-Miralles, Eladio A. Velasco, Nagarajan Paramasivam, Matthias Schlesner, Abhishek Kumar, Ying Yuan, Jan Lubinski, Obul Reddy Bandapalli, Kari Hemminki, Asta Foersti
Summary: Whole-genome sequencing and functional characterization studies on colorectal cancer families identified CYBA and TRPM4 as candidate predisposition genes that mechanistically involve intestinal barrier integrity through reactive oxygen species and mucus biology, converging in chronic bowel inflammation, a known risk factor for colorectal cancer.
Article
Multidisciplinary Sciences
Richard Barfield, Conghui Qu, Robert S. Steinfelder, Chenjie Zeng, Tabitha A. Harrison, Stefanie Brezina, Daniel D. Buchanan, Peter T. Campbell, Graham Casey, Steven Gallinger, Marios Giannakis, Stephen B. Gruber, Andrea Gsur, Li Hsu, Jeroen R. Huyghe, Victor Moreno, Polly A. Newcomb, Shuji Ogino, Amanda I. Phipps, Martha L. Slattery, Stephen N. Thibodeau, Quang M. Trinh, Amanda E. Toland, Thomas J. Hudson, Wei Sun, Syed H. Zaidi, Ulrike Peters
Summary: This study assessed the associations between germline variations and somatic events in colorectal cancer (CRC) through two complementary approaches. The analysis revealed that a germline variant located within a CNV region associated with TLR3 was also associated with a non-silent mutation within the FBXW7 gene. Additionally, a germline variant located in the CDX1/PDGFRB gene frequently gained/lost in colorectal tumors was found to be associated with overall CRC risk.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Questa Karlsson, Mark N. Brook, Tokhir Dadaev, Sarah Wakerell, Edward J. Saunders, Kenneth Muir, David E. Neal, Graham G. Giles, Robert J. MacInnis, Stephen N. Thibodeau, Shannon K. McDonnell, Lisa Cannon-Albright, Manuel R. Teixeira, Paula Paulo, Marta Cardoso, Chad Huff, Donghui Li, Yu Yao, Paul Scheet, Jennifer B. Permuth, Janet L. Stanford, James Y. Dai, Elaine A. Ostrander, Olivier Cussenot, Geraldine Cancel-Tassin, Josef Hoegel, Kathleen Herkommer, Johanna Schleutker, Teuvo L. J. Tammela, Venkat Rathinakannan, Csilla Sipeky, Fredrik Wiklund, Henrik Gronberg, Markus Aly, William B. Isaacs, Jo L. Dickinson, Liesel M. FitzGerald, Melvin L. K. Chua, Tu Nguyen-Dumont, Practical Consortium, Daniel J. Schaid, Melissa C. Southey, Rosalind A. Eeles, Zsofia Kote-Jarai
Summary: The study suggests that carriers of germline ATM mutations have an increased risk of prostate cancer, especially those with tier 1 variants. Additionally, patients diagnosed at a younger age tend to have higher frequencies of tier 1 variants.
EUROPEAN UROLOGY ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Pingping Xu, Danfeng Sun, Yaqi Gao, Yi Jiang, Ming Zhong, Gang Zhao, Jinxian Chen, Zheng Wang, Qiang Liu, Jie Hong, Haoyan Chen, Ying-Xuan Chen, Jing-Yuan Fang
Summary: Through whole-exome sequencing, we identified mutations in genes related to the Fanconi anemia DNA repair pathway in familial colorectal cancer patients, including CHEK2. Further experiments showed that CHEK2 plays a crucial role in cell cycle and DNA damage repair processes.
Article
Health Care Sciences & Services
Emily P. Slater, Lisa M. Wilke, Lutz Benedikt Boehm, Konstantin Strauch, Manuel Lutz, Norman Gercke, Elvira Matthai, Kari Hemminki, Asta Forsti, Matthias Schlesner, Nagarajan Paramasivam, Detlef K. Bartsch
Summary: Familial pancreatic cancer (FPC) is a rare inherited tumor syndrome, with an unclear genetic basis of disease susceptibility in most FPC families beyond known predisposition genes BRCA1/2, CDKN2A and PALB2. Whole-genome sequencing revealed potential predisposing candidate genes, supporting the hypothesis that FPC is a highly heterogeneous polygenetic disease caused by low-frequency or rare variants.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Oncology
Owen J. Chen, Ester Castellsague, Mohamed Moustafa-Kamal, Javad Nadaf, Barbara Rivera, Somayyeh Fahiminiya, Yilin Wang, Isabelle Gamache, Caterina Pacifico, Lai Jiang, Jian Carrot-Zhang, Leora Witkowski, Albert M. Berghuis, Stefan Schoenberger, Dominik Schneider, Morten Hillmer, Susanne Bens, Reiner Siebert, Colin J. R. Stewart, Ziguo Zhang, William C. H. Chao, Celia M. T. Greenwood, David Barford, Marc Tischkowitz, Jacek Majewski, William D. Foulkes, Jose G. Teodoro
Summary: Two germline CDC20 missense variants that segregate with cancer in two families compromise the spindle assembly checkpoint and lead to aberrant mitotic progression, which could predispose cells to transformation.
Article
Oncology
Karolin Bucksch, Silke Zachariae, Aysel Ahadova, Stefan Aretz, Reinhard Buttner, Heike Goergens, Elke Holinski-Feder, Robert Hueneburg, Matthias Kloor, Magnus Knebel Doeberitz, Swetlana Ladigan-Badura, Gabriela Moeslein, Monika Morak, Jacob Nattermann, Huu Phuc Nguyen, Claudia Perne, Silke Redler, Ariane Schmetz, Verena Steinke-Lange, Harald Surowy, Deepak B. Vangala, Juergen Weitz, Markus Loeffler, Christoph Engel
Summary: This study aimed to characterize and compare the risks for adenoma and CRC in Lynch syndrome (LS), Lynch-like syndrome (LLS) and familial colorectal cancer type X (FCCX). The study found similar risks for colorectal adenomas, but different risks for first and metachronous CRC between the three risk groups, with CRC risk highest in LS, followed by LLS and lowest in FCCX. Male sex and a prevalent adenoma in the index colonoscopy were associated with a higher risk for incident adenoma and CRC.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Genetics & Heredity
Ashish Kumar Singh, Bente Talseth-Palmer, Alexandre Xavier, Rodney J. Scott, Finn Drablos, Wenche Sjursen
Summary: This study aimed to identify high-penetrant and low-penetrant genetic variants associated with familial colorectal cancer. Whole exome sequencing was performed and several causative and potentially causative germline variants in genes known for their association with colorectal cancer were identified. Additionally, variants in genes not typically associated with colorectal cancer were also found, suggesting a larger genetic spectrum of this disease.
BMC MEDICAL GENOMICS
(2023)
Article
Biochemistry & Molecular Biology
Diamanto Skopelitou, Aayushi Srivastava, Beiping Miao, Abhishek Kumar, Dagmara Dymerska, Nagarajan Paramasivam, Matthias Schlesner, Jan Lubinski, Kari Hemminki, Asta Foersti, Obul Reddy Bandapalli
Summary: In this study, two novel variants in the SLC15A4 gene were identified using whole exome sequencing and a familial cancer variant prioritization pipeline, suggesting the involvement of SLC15A4 in the genetic inheritance of familial colorectal cancer for the first time.
MOLECULAR GENETICS AND GENOMICS
(2022)
Article
Multidisciplinary Sciences
Stephanie U. Greer, Jiamin Chen, Margret H. Ogmundsdottir, Carlos Ayala, Billy T. Lau, Richard Glenn C. Delacruz, Imelda T. Sandoval, Sigrun Kristjansdottir, David A. Jones, Derrick S. Haslem, Robin Romero, Gail Fulde, John M. Bell, Jon G. Jonasson, Eirikur Steingrimsson, Hanlee P. Ji, Lincoln D. Nadauld
Summary: This article investigates the role of autophagy related gene ATG7 in cholangiocarcinoma. The study finds that germline variants and somatic deletions of ATG7 are associated with the development of cholangiocarcinoma, and these variants impact the function of autophagy.
SCIENTIFIC REPORTS
(2022)
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)
Article
Oncology
Hannah M. Seagle, Samantha R. Keller, Sean V. Tavtigian, Carolyn Horton, Andreana N. Holowatyj
Summary: Germline genetic predisposition in early-onset colorectal cancer (EOCRC) varies across racial/ethnic groups. Current multigene panel tests may not accurately assess the risk of EOCRC in diverse populations.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Riyue Bao, Anita Ng, Mark Sasaki, Myvizhi Esai Selvan, Alyna Katti, Hyesan Lee, Lei Huang, Andrew D. Skol, Cinzia Lavarino, Hector Salvador, Robert J. Klein, Zeynep H. Gumus, Jaume Mora, Kenan Onel
Summary: Whole-exome sequencing in a Spanish and Catalan family revealed a rare germline variant in ERBB2 associated with familial cancer risk. Functional assays showed that this variant activates ERBB2 signaling, increasing the risk of cancer.
CANCER PREVENTION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Beiping Miao, Diamanto Skopelitou, Aayushi Srivastava, Sara Giangiobbe, Dagmara Dymerska, Nagarajan Paramasivam, Abhishek Kumar, Magdalena Kuswik, Wojciech Kluzniak, Katarzyna Paszkowska-Szczur, Matthias Schlesner, Jan Lubinski, Kari Hemminki, Asta Foersti, Obul Reddy Bandapalli
Summary: In this study, a novel germline variant in the PTK7 gene associated with genetic predisposition to colorectal cancer was identified through whole-exome sequencing. Further investigations revealed the oncogenic function of PTK7, including increased cell proliferation, migration, and invasion, inhibition of apoptosis pathways, and activation of AKT signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Yanyang Zhao, Tian Yu, Jie Sun, Feiliang Wang, Chaoze Cheng, Shurong He, Lan Chen, Donghui Xie, Liping Fu, Xuhuizi Guan, An Yan, Yao Li, Gang Miao, Xiaoquan Zhu
Summary: The study identified WDR77 mutations associated with predisposition to nonsyndromic familial papillary thyroid cancer, where a rare heterozygous missense mutation in one family impairs the interaction of WDR77 with PRMT5, and a splice-site mutation in another family results in a marked decrease in H4R3me2 levels. These findings provide new insights into the genetic factors influencing thyroid cancer susceptibility.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Editorial Material
Oncology
Armin Zebisch, Heinz Sill
EXPERT REVIEW OF ANTICANCER THERAPY
(2022)
Letter
Oncology
Markus G. Seidel, Luka Brcic, Gerald Hoefler, Caroline Hutter, Milen Minkov, Laura Sophie Steffen, Armin Zebisch, Martin Benesch
PEDIATRIC BLOOD & CANCER
(2023)
Letter
Hematology
Noemi Meszaros, Karin Lind, Robert Sehlke, Bojan Vilagos, Nikolaus Krall, Gregory I. Vladimer, Heinz Sill
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Johannes Fosselteder, Gabriel Pabst, Tommaso Sconocchia, Angelika Schlacher, Lisa Auinger, Karl Kashofer, Christine Beham-Schmid, Slave Trajanoski, Claudia Waskow, Wolfgang Schoell, Heinz Sill, Armin Zebisch, Albert Woelfler, Daniel Thomas, Andreas Reinisch
Summary: This study established a human gene-engineered model of CALR mutation-associated MPN using CRISPR/Cas9 and adeno-associated viral vector-mediated knock-in strategy, which recapitulates the disease characteristics and reveals mutation-specific vulnerabilities with preferential sensitivity of CALR mutant cells to inhibition of the BiP chaperone and the proteasome. This humanized model provides a useful platform for testing novel therapeutic strategies in a human setting.
Review
Genetics & Heredity
Tina Moser, Stefan Kuehberger, Isaac Lazzeri, Georgios Vlachos, Ellen Heitzer
Summary: Liquid biopsies (LBs), especially using circulating tumor DNA (ctDNA), have the potential to revolutionize precision oncology and blood-based cancer screening. Recent advancements in technology and understanding of cell-free DNA (cfDNA) biology have allowed for the detection of tumor-specific changes with high resolution, including new analysis concepts such as methylomics, fragmentomics, and nucleosomics. Machine learning (ML) algorithms are increasingly being utilized to extract disease- and tissue-specific signals from cfDNA due to the large number of markers and complexity of the data. This review provides insights into the biological features of ctDNA and its incorporation into sophisticated ML applications.
TRENDS IN GENETICS
(2023)
Article
Genetics & Heredity
Julia Vodopiutz, Lisa-Maria Steurer, Florentina Haufler, Franco Laccone, Dorota Garczarczyk-Asim, Matthias Hilkenmeier, Philipp Steinbauer, Andreas R. Janecke
Summary: SHOX deficiency is a common genetic cause of short stature. It can lead to Leri-Weill dyschondrosteosis and nonspecific short stature. This study reports the pseudo-autosomal recessive inheritance of Leri-Weill dyschondrosteosis in two siblings caused by a novel homozygous non-canonical splice-site variant in the SHOX gene. This study expands the understanding of the molecular and inheritance spectrum of SHOX deficiency.
Article
Biochemistry & Molecular Biology
Yihe Wang, Astrid Hammer, Gerald Hoefler, Ernst Malle, Clare L. Hawkins, Christine Y. Chuang, Michael J. Davies
Summary: Atherosclerosis is a chronic inflammatory disease characterized by plaque formation in arterial walls. The study found that hypochlorous acid (HOCl) and chloramines can specifically modify aggrecan, a proteoglycan involved in atherogenesis. These modifications, different from those induced by ADAMTS1, can lead to irreversible protein cross-links. The findings also showed colocalization of aggrecan and HOCl-generated epitopes in advanced human atherosclerotic plaques.
Review
Hematology
Eduard Schulz, Peter D. Aplan, Sylvie D. Freeman, Steven Z. Pavletic
Summary: Approximately 90% of MDS patients have oncogenic somatic mutations, and the genetic risk stratification and diagnosis criteria have improved. Monitoring MRD has been used in leukemias but not yet defined for MDS. This article discusses the evidence, challenges, and framework for integrating MRD into MDS treatment and clinical trials.
Article
Biology
Georg Richtig, Melanie Kienzl, Sonja Rittchen, David Roula, Juergen Eberle, Zina Sarif, Martin Pichler, Gerald Hoefler, Akos Heinemann
Summary: This study aimed to investigate the pro-apoptotic effects of cannabinoids in metastatic melanoma and their value besides conventional targeted therapy. The results showed that cannabinoids can induce apoptosis through the mitochondrial cytochrome c release and caspase activation pathway, and do not interfere with commonly used targeted therapy.
Article
Biophysics
David Beshensky, Filip Pirsl, Noa G. Holtzman, Seth M. Steinberg, Jacqueline W. Mays, Edward W. Cowen, Leora E. Comis, Galen O. Joe, M. Teresa Magone, Eduard Schulz, Meryl A. Waldman, Steven Z. Pavletic
Summary: The study aimed to investigate kidney complications in patients with chronic graft-versus-host disease (cGVHD). The research found that kidney dysfunction was present in a subgroup of cGVHD patients, with some specific factors associated with this dysfunction. It was also observed that kidney dysfunction was linked to lower overall survival in these patients, highlighting the significance of addressing this complication. The study suggests that the etiology of kidney dysfunction in cGVHD patients may be unrelated to the disease itself but potentially caused by drug-related toxicities.
BONE MARROW TRANSPLANTATION
(2023)
Article
Biophysics
Aaron T. Zhao, Filip Pirsl, Seth M. Steinberg, Noa G. Holtzman, Eduard Schulz, Alain Mina, Jacqueline W. Mays, Edward W. Cowen, Leora E. Comis, Galen O. Joe, Jack A. Yanovski, Steven Z. Pavletic
Summary: The prevalence and impact of metabolic syndrome (MetS) in patients with chronic graft-versus-host disease (cGVHD) remain unknown. A cross-sectional study found that a majority of cGVHD patients met the diagnostic criteria for MetS. Higher body mass index, lower performance status scores, and certain blood markers were associated with MetS. However, patients with MetS did not have different survival rates or severity of cGVHD compared to patients without MetS. Screening for MetS in cGVHD patients is important to prevent complications.
BONE MARROW TRANSPLANTATION
(2023)
Letter
Oncology
Tommaso Sconocchia, Johannes Fosselteder, Lisa Auinger, Erdem Oezkaya, Theresa Benezeder, Magdalena Lang, Christine Beham-Schmid, Gerald Hoefler, Armin Zebisch, Albert Woelfler, Heinz Sill, Peter Wolf, Herbert Strobl, Andreas Reinisch
Article
Genetics & Heredity
Ferda O. Hosnut, Andreas R. Janecke, Gulseren Sahin, Georg F. Vogel, Naz G. Lafci, Paul Bichler, Thomas Mueller, Lukas A. Huber, Taras Valovka, Aysel U. Aksu
Summary: Congenital glucose-galactose malabsorption is a rare autosomal recessive disorder caused by mutations in SLC5A1 gene. Our study reports clinical and molecular data from 11 affected individuals in four unrelated Turkish families. Two novel SLC5A1 missense variants, p.Gly43Arg and p.Ala92Val, were identified in two families and linked to the disease. Our findings expand the mutational spectrum of this rare disorder.
