Article
Genetics & Heredity
Liam F. Spurr, Ralph R. Weichselbaum, Sean P. Pitroda
Summary: This study demonstrates that tumor aneuploidy could serve as an independent prognostic indicator in patients with low tumor mutational burden (TMB) receiving immunotherapy.
Article
Biotechnology & Applied Microbiology
Shaolong Cao, Jennifer R. Wang, Shuangxi Ji, Peng Yang, Yaoyi Dai, Shuai Guo, Matthew D. Montierth, John Paul Shen, Xiao Zhao, Jingxiao Chen, Jaewon James Lee, Paola A. Guerrero, Nicholas Spetsieris, Nikolai Engedal, Sinja Taavitsainen, Kaixian Yu, Julie Livingstone, Vinayak Bhandari, Shawna M. Hubert, Najat C. Daw, P. Andrew Futreal, Eleni Efstathiou, Bora Lim, Andrea Viale, Jianjun Zhang, Matti Nykter, Bogdan A. Czerniak, Powel H. Brown, Charles Swanton, Pavlos Msaouel, Anirban Maitra, Scott Kopetz, Peter Campbell, Terence P. Speed, Paul C. Boutros, Hongtu Zhu, Alfonso Urbanucci, Jonas Demeulemeester, Peter Van Loo, Wenyi Wang
Summary: This study presents a method to quantify tumor-specific total mRNA expression from bulk sequencing data and validates it in various cancer types. High total mRNA expression is associated with increased risk of disease progression and death. The expression is influenced by cancer-specific gene alteration, intra-tumor genetic heterogeneity, and pan-cancer trends in metabolic dysregulation.
NATURE BIOTECHNOLOGY
(2022)
Article
Oncology
Tao Qing, Xinfeng Wang, Tomi Jun, Li Ding, Lajos Pusztai, Kuan-Lin Huang
Summary: The study found that, in addition to a handful of known pathogenic variants such as BRCA1/2, other genomic events including mutations in ATM and ATR genes can also cause HRD. Different cancer types include tumor subsets that show HRD phenotype, suggesting the potential broader utility of PARPi for cancers with a wide range of genomic alterations.
Article
Multidisciplinary Sciences
Musalula Sinkala
Summary: This study analyzes the genomic sequences of 20,331 primary tumors, identifying driver mutations in 727 known cancer genes and revealing significant variations in mutation frequency and co-occurrence in different cancer types. The study also finds that patients with tumors displaying different combinations of gene mutation patterns have variable survival outcomes, providing new insights into the genetic landscape and mechanisms of cancer development.
SCIENTIFIC REPORTS
(2023)
Article
Biochemical Research Methods
Zubair Lalani, Gillian Chu, Silas Hsu, Shaw Kagawa, Michael Xiang, Simone Zaccaria, Mohammed El-Kebir
Summary: Copy-number aberrations (CNAs) are common genetic alterations in cancer, but their identification from DNA sequencing data is challenging. Existing segmentation algorithms have limitations, so we introduce CNAViz, a web-based tool that allows the user to perform both local and global segmentation, improving the accuracy of the segmentation.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Oncology
Abhilasha Sinha, Yong Zou, Ayushi S. Patel, Seungyeul Yoo, Feng Jiang, Takashi Sato, Ranran Kong, Hideo Watanabe, Jun Zhu, Pierre P. Massion, Alain C. Borczuk, Charles A. Powell
Summary: This study found that MDM2 amplification and overexpression are associated with invasiveness and poor survival in lung adenocarcinoma. MDM2-targeted therapy effectively suppresses cell proliferation, migration, and invasion in cells with MDM2 amplification/overexpression, but not in cells without MDM2 amplification. Additionally, RNA sequencing identified different signaling pathways affected by MDM2-targeted therapy based on the p53 status of lung adenocarcinoma cells.
Article
Oncology
Lisui Bao, Xiaoming Zhong, Yang Yang, Lixing Yang
Summary: Bao et. al. developed an algorithm called Starfish to identify six signatures of complex genomic rearrangements in human cancer genomics datasets, with a notable pattern called hourglass chromothripsis found in prostate cancer. The study analyzed 2,014 CGRs from 2,428 whole-genome-sequenced tumors and discovered six CGR signatures based on copy number and breakpoint patterns, with over half belonging to previously unreported signatures.
Article
Oncology
Samuel Terkper Ahuno, Anna-Lisa Doebley, Thomas U. Ahearn, Joel Yarney, Nicholas Titiloye, Nancy Hamel, Ernest Adjei, Joe-Nat Clegg-Lamptey, Lawrence Edusei, Baffour Awuah, Xiaoyu Song, Verna Vanderpuye, Mustapha Abubakar, Maire Duggan, Daniel G. Stover, Kofi Nyarko, John M. S. Bartlett, Francis Aitpillah, Daniel Ansong, Kevin L. Gardner, Felix Andy Boateng, Anne M. Bowcock, Carlos Caldas, William D. Foulkes, Seth Wiafe, Beatrice Wiafe-Addai, Montserrat Garcia-Closas, Alexander Kwarteng, Gavin Ha, Jonine D. Figueroa, Paz Polak
Summary: ctDNA sequencing studies conducted on patients in sub-Saharan Africa revealed the detection of ctDNA in a majority of patients, despite not being selected for tumor grade and subtype. Additionally, breast cancer driver copy number alterations were observed in the majority of patients.
NPJ PRECISION ONCOLOGY
(2021)
Article
Biochemical Research Methods
Zuhal Ozcan, Francis A. San Lucas, Justin W. Wong, Kyle Chang, Konrad H. Stopsack, Jerry Fowler, Yasminka A. Jakubek, Paul Scheet
Summary: This study presents a statistical approach that utilizes RNA-seq data to detect somatic copy number alterations (SCNAs) in human cancers without the need for DNA sequencing. The results demonstrate that the RNA-based method has high sensitivity and specificity for detecting SCNAs, and successfully replicated SCNA features associated with breast cancer subtypes. This suggests that the method has potential for detecting SCNAs in clinical and population-based settings.
Article
Multidisciplinary Sciences
Ming Tang, Hussein A. Abbas, Marcelo V. Negrao, Maheshwari Ramineni, Xin Hu, Shawna Marie Hubert, Junya Fujimoto, Alexandre Reuben, Susan Varghese, Jianhua Zhang, Jun Li, Chi-Wan Chow, Xizeng Mao, Xingzhi Song, Won-Chul Lee, Jia Wu, Latasha Little, Curtis Gumbs, Carmen Behrens, Cesar Moran, Annikka Weissferdt, J. Jack Lee, Boris Sepesi, Stephen Swisher, Chao Cheng, Jonathan Kurie, Don Gibbons, John V. Heymach, Ignacio I. Wistuba, P. Andrew Futreal, Neda Kalhor, Jianjun Zhang
Summary: The authors analyzed lung cancers of mixed histology and found that histologic subtypes are associated with transcriptomic features rather than genomic profiles in most tumors. This suggests that the molecular determinants of lung cancer histologic subtypes are not well understood.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Mulong Du, Dongying Gu, Junyi Xin, Ulrike Peters, Mingyang Song, Guoshuai Cai, Shuwei Li, Shuai Ben, Yixuan Meng, Haiyan Chu, Lianmin Chen, Qianghu Wang, Lingjun Zhu, Zan Fu, Zhengdon Zhang, Meilin Wang
Summary: In this study, the genome, epigenome, transcriptome, and proteome of tumors from Chinese colorectal cancer patients were analyzed. The findings showed that early-onset colorectal cancer has a high tumor mutation burden, increased DNA repair features, and immune infiltration. The study also identified LMTK3 as a potential biomarker and functional modulator in the development and immunotherapy of early-onset colorectal cancer. This integrative omics study provides valuable knowledge for precision oncology of colorectal cancer.
CELL REPORTS MEDICINE
(2023)
Article
Oncology
Karl Kashofer, Sigrid Regauer, Olaf Reich, Edgar Petru, Elke Winter
Summary: This study evaluated the prevalence of somatic gene mutations in different stages of cervical carcinogenesis, finding that activating oncogenic gene mutations, particularly in the PIK3CA gene, occur early in the development of cervical cancer. The mutational status is not prognostically relevant in micro-invasive cervical squamous cell carcinoma.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lizhu Liu, Lihong Wu, Dan Shan, Bo Han
Summary: This study investigated the copy number variation (CNV) of the PDGFRA pathway in different cancer types and found that CNV gain in the PDGFRA pathway is associated with shorter overall survival in cancer patients. Furthermore, CN gain is accompanied by changes in other factors such as LOH, CNV burden, and tumor-infiltrating immune cell populations. The enrichment of tumor-related signaling pathways also differs between the CN gain and No CN gain groups.
MOLECULAR GENETICS AND GENOMICS
(2022)
Article
Cell Biology
Ilda Patricia Ribeiro, Luisa Esteves, Francisco Caramelo, Isabel Marques Carreira, Joana Barbosa Melo
Summary: This study identified a nine-gene multi-omics signature correlated with the survival of HNC patients, independently of relapse or metastasis. This finding represents a significant step forward in improving patient management and guiding the development of new therapeutic targets.
Review
Neurosciences
Timothy E. Richardson, Jamie M. Walker, Kalil G. Abdullah, Samuel K. McBrayer, Mariano S. Viapiano, Zarmeen M. Mussa, Nadejda M. Tsankova, Matija Snuderl, Kimmo J. Hatanpaa
Summary: Chromosomal instability (CIN) is a fundamental property of cancer and a key mechanism of tumorigenesis and progression. It is found in various cancers and is associated with poor clinical outcomes. However, there have been relatively few studies on this process, mainly due to the difficulty of measuring it clinically.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Oncology
Jos B. Poell, Leon J. Wils, Arjen Brink, Ralf Dietrich, Christine Krieg, Eunike Velleuer, Ilkay Evren, Elisabeth R. Brouns, Jan G. de Visscher, Elisabeth Bloemena, Bauke Ylstra, Ruud H. Brakenhoff
Summary: This study developed a noninvasive genetic assay to detect genetically altered fields in the oral cavity. The assay demonstrated high accuracy and predicted the development of oral squamous cell carcinoma in high-risk individuals. This method can be used for cancer screening in high-risk populations and to map the extent of lesions beyond what is visible.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Sanne ten Hoorn, Linda Mol, Dirkje W. Sommeijer, Lisanne Nijman, Tom van den Bosch, Tim R. de Back, Bauke Ylstra, Erik van Dijk, Carel J. M. van Noesel, Roy J. Reinten, Iris D. Nagtegaal, Miriam Koopman, Cornelis J. A. Punt, Louis Vermeulen
Summary: We evaluated the potential efficacy of adding anti-EGFR therapy to anti-VEGF therapy in a subgroup of patients with metastatic colorectal cancer. The retrospective study (CAIRO2 trial, n = 736) showed no benefit of anti-EGFR addition within the subgroup, but an overall survival increase of 6.5 months compared to the original trial.
CLINICAL COLORECTAL CANCER
(2023)
Article
Oncology
Colin Y. C. Lee, Adriaan Olivier, Judith Honing, Anne-Marie Lydon, Susan Richardson, Maria O'Donovan, Marc Tischkowitz, Rebecca C. Fitzgerald, Massimiliano di Pietro
Summary: Hereditary diffuse gastric cancer, caused by CDH1 gene mutations, is characterized by early-onset signet ring cell carcinoma. Prophylactic total gastrectomy is the recommended treatment. This study assessed different sampling strategies for detecting signet ring cell carcinoma and identified criteria for characterizing endoscopic lesions in hereditary diffuse gastric cancer.
Article
Oncology
G. Tjitske Los-de Vries, Phylicia Stathi, Ryanne Rutkens, Nathalie J. Hijmering, Jeroen A. C. W. Luijks, Patricia J. T. A. Groenen, Daphne de Jong, Bauke Ylstra, Margaretha G. M. Roemer
Summary: Primary and relapsed LBCL-IP have a common set of genetic alterations that support survival and proliferation, providing insight into the disease progression.
Article
Oncology
Anna Lena van Gulik, Ellen Sluydts, Liesbet Vervoort, Mark Kockx, Pim Kortman, Bauke Ylstra, Stephen P. Finn, Lukas Bubendorf, Idris Bahce, Daoud Sie, Teodora Radonic, Birgit Lissenberg-Witte, Erik Thunnissen
Summary: This study investigates the impact of cell size and ploidy on FISH results. The results show that in liver cell nuclei, the number of FISH signals increases with nuclear size and section thickness. In non-small cell lung cancer cases, tumor cells with higher ploidy levels and nuclear size have an increased chance of single signals. In addition, no rearrangements were found in lung cancer samples with borderline ALK FISH results, proving a false positive result.
TRANSLATIONAL LUNG CANCER RESEARCH
(2023)
Letter
Hematology
Wendy B. C. Stevens, G. Tjitske Los-de Vries, Carole Langois-Jacques, Andrew J. Clear, Phylicia Stathi, Birgitta Sander, Andreas Rosenwald, Maria Calaminici, Eva Hoster, Wolfgang Hiddemann, Philippe Gaulard, Gilles Salles, Wolfram Klapper, Luc Xerri, Catherine Burton, Reuben M. Tooze, Alexandra G. Smith, Christian Buske, David W. Scott, Yasodha Natkunam, Ranjana Advani, Laurie H. Sehn, John Raemaekers, John Gribben, Sandra Lockmer, Eva Kimby, Marie Jose Kersten, Delphine Maucort-Boulch, Bauke Ylstra, Erik van Dijk, Daphne de Jong
Article
Hematology
Patricia Johansson, Stefan Alig, Julia Richter, Christine Hanoun, Jan Rekowski, Jan Duerig, Bauke Ylstra, Daphne de Jong, Wolfram Klapper, Ash A. Alizadeh, Ulrich Duehrsen, Andreas Huettmann
Summary: In DLBCL, a positive interim PET scan predicts treatment failure, and combining it with the presence of an IgM gammopathy can improve prediction. The combination of interim PET and IgM gammopathy can dichotomize the population into high-risk and low-risk groups with significantly different outcomes. Only the interim PET result and IgM gammopathy status were significantly associated with outcome, making them important factors in risk-adapted treatment strategies.
ANNALS OF HEMATOLOGY
(2023)
Editorial Material
Hematology
Bauke Ylstra, Daphne de Jong
Summary: In this study, the authors demonstrate the usefulness of a dark zone signature (DZsig) for diagnosing aggressive B-cell lymphoma with DLBCL morphology, and highlight its strong prognostic value.
Article
Pathology
Tanya T. D. Soeratram, Hedde D. Biesma, Jacqueline M. P. Egthuijsen, Elma Meershoek-Klein Kranenbarg, Henk H. Hartgrink, Cornelis J. H. van de Velde, Aart Mookhoek, Erik van Dijk, Yongsoo Kim, Bauke Ylstra, Hanneke W. M. van Laarhoven, Nicole C. T. van Grieken
Summary: Tumor-infiltrating lymphocytes are important for the survival of gastric cancer patients, and T-cell densities in different regions of the tumor can serve as prognostic markers. CD8OIM and FOXP3TC are identified as key factors for survival, and the combination of their densities can stratify patients into distinct subgroups with different prognosis. These immune subgroups are independent predictors for cancer-specific survival in resectable gastric cancer.
Article
Multidisciplinary Sciences
Margaretha G. M. Roemer, Tim van de Brug, Erik Bosch, Daniella Berry, Nathalie Hijmering, Phylicia Stathi, Karin Weijers, Jeannette Doorduijn, Jacoline Bromberg, Mark van de Wiel, Bauke Ylstra, Daphne de Jong, Yongsoo Kim
Summary: In order to understand the clinical relevance of the tumor microenvironment (TME), it is important to study the interactions between malignant and non-malignant cells in clinical samples. Researchers have developed a computational framework to comprehensively analyze the spatial context of the TME, including close and long-distance interactions between different cell types. This framework was applied to imaging data from 88 primary central nervous system lymphomas, revealing significant prognostic subgroups mainly determined by the spatial context. The results highlight the importance of spatial context in predicting patient survival, particularly in relation to macrophage infiltration near specific cell types.
Article
Medicine, Research & Experimental
Ymke van Der Pol, Normastuti Adhini Tantyo, Nils Evander, Anouk E. Hentschel, Birgit M. M. Wever, Jip Ramaker, Sanne Bootsma, Marieke F. Fransen, Kristiaan J. Lenos, Louis Vermeulen, Famke L. Schneiders, Idris Bahce, Jakko A. Nieuwenhuijzen, Renske D. M. Steenbergen, D. Michiel Pegtel, Norbert Moldovan, Florent Mouliere
Summary: This study demonstrates the use of Oxford Nanopore Technologies (ONT) sequencing to obtain genomic and fragmentomic data from liquid biopsies. The results show that copy number aberrations and cfDNA fragmentation patterns can be determined in less than 24 hours. Furthermore, ONT sequencing allows analysis of previously understudied cfDNA populations.
EMBO MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Kieran Foley, David Shorthouse, Eric Rahrmann, Lizhe Zhuang, Ginny Devonshire, Rebecca C. OCCAMS Consortium, Rebecca C. Fitzgerald, Benjamin A. Hall
Summary: Metastasis in oesophageal adenocarcinoma (OAC) is a crucial factor affecting survival. Radiological staging is commonly used to assess metastases, but its accuracy is limited. This study analyzed lymph node metastases and identified new roles of genes SMAD4 and KCNQ3 in metastasis. The findings suggest that both genes could serve as novel biomarkers for metastatic risk and offer potential new targets for drug treatment.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)