Article
Cell Biology
Dong-Min Shi, Shuang-Shuang Dong, Hong-Xing Zhou, Dong-Qiang Song, Jin-Liang Wan, Wei-Zhong Wu
Summary: Metastasis is a key event in the rapid relapse and death of HCC patients after surgery. TP53, MYO5A, ROS1, and ARID2 were identified as prominent mutants in HCC cells. Different mutations occurred at different stages during HCC progression, and certain mutations were unique to specific metastatic tropisms. Gene expression levels of PER1, LMO2, GAS7, and NR4A3 were positively associated with relapse-free survival of HCC patients. Integrated analysis revealed genes with both somatic mutations and dysregulated mRNA levels in high metastatic cells.
CELLULAR SIGNALLING
(2023)
Article
Multidisciplinary Sciences
Timothy Pyrkov, Konstantin Avchaciov, Andrei E. Tarkhov, Leonid Menshikov, Andrei Gudkov, Peter O. Fedichev
Summary: By analyzing CBC measurements, researchers found that the distribution of the dynamic organism state indicator (DOSI) widens with age, which can be explained by the gradual loss of DOSI autocorrelation time. Independent analysis also showed that at the critical point of 120-150 years, DOSI recovery time and variance will diverge simultaneously, corresponding to a complete loss of resilience.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Davidson Zhao, Entsar Eladl, Mojgan Zarif, Jose-Mario Capo-Chichi, Andre Schuh, Eshetu Atenafu, Mark Minden, Hong Chang
Summary: This study retrospectively evaluated 266 AML-MRC patients and found that TP53(MUT) AML-MRC is a very-high-risk subtype of AML with poor prognosis. Patients with high TP53(MUT) variant allele frequency had worse outcomes. TP53 mutations and elevated serum LDH were independent predictors for inferior prognosis.
Article
Multidisciplinary Sciences
Yukinari Haraoka, Yuki Akieda, Yuri Nagai, Chihiro Mogi, Tohru Ishitani
Summary: The study demonstrates that oncogenic cells can be eliminated through oncogene-induced senescence, but this behavior can be altered by a p53 mutation, leading to promotion rather than suppression of tumorigenesis. The findings provide important insights into the initial step of tumor formation.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Netta Makinen, Meng Zhou, Zhouwei Zhang, Yosuke Kasai, Elizabeth Perez, Grace E. Kim, Chrissie Thirlwell, Eric Nakakura, Matthew Meyerson
Summary: This study reveals the major genomic diversity among multifocal ileal NETs, showing that synchronous primary tumors within each patient develop independently with different somatic variations. Additionally, tumors from the same patient can gain or lose different parental alleles, emphasizing the need to identify and remove all primary tumors to prevent metastasis and to optimize targeted treatments.
Article
Allergy
Tomohisa Iinuma, Masahiro Kiuchi, Kiyoshi Hirahara, Junya Kurita, Kota Kokubo, Hiroyuki Yagyu, Riyo Yoneda, Tomoyuki Arai, Yuri Sonobe, Masaki Fukuyo, Atsushi Kaneda, Syuji Yonekura, Toshinori Nakayama, Yoshitaka Okamoto, Toyoyuki Hanazawa
Summary: This study comprehensively investigated the role and changes of antigen-specific T cells in Japanese cedar pollinosis patients before and after sublingual immunotherapy (SLIT). The results revealed that SLIT led to clonal expansion and differentiation of T(H)2 cells, as well as differentiation of trans-type T(H)2 cells into regulatory T cells. The study also identified musculin (MSC) as a potential biomarker of SLIT for allergic rhinitis.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Tanya T. Karagiannis, Todd W. Dowrey, Carlos Villacorta-Martin, Monty Montano, Eric Reed, Anna C. Belkina, Stacy L. Andersen, Thomas T. Perls, Stefano Monti, George J. Murphy, Paola Sebastiani
Summary: By analyzing single cell RNA sequencing data from seven centenarians, researchers have found that these individuals possess unique and highly functional immune systems that may contribute to their exceptional longevity.
Article
Oncology
Daniel J. Craig, Erin L. Crawford, Heidi Chen, Eric L. Grogan, Steven A. Deppen, Thomas Morrison, Sanja L. Antic, Pierre P. Massion, James C. Willey
Summary: A biomarker, characterized by TP53 somatic mutations in airway epithelial cells, has been discovered to accurately determine lung cancer risk. The prevalence of TP53 mutations was significantly associated with cancer status, and combining it with other factors improved risk assessment accuracy.
Article
Environmental Sciences
Hua Chen, Anqi Song, Faisal UL Rehman, Dan Han
Summary: Despite significant advancements in cancer research, the outcomes for lung cancer patients are still unsatisfactory. In this study, we utilized single-cell RNA sequencing to identify and characterize the cellular heterogeneity within the lung cancer microenvironment. Our findings revealed distinct cell types and their interplay, identified potential predictive biomarkers, and shed light on the immune response within the tumor microenvironment. These findings contribute to our understanding of cancer heterogeneity and have implications for the development of targeted therapies.
ENVIRONMENTAL TOXICOLOGY
(2023)
Article
Genetics & Heredity
Ryan N. Doan, Michael B. Miller, Sonia N. Kim, Rachel E. Rodin, Javier Ganz, Sara Bizzotto, Katherine S. Morillo, August Yue Huang, Reethika Digumarthy, Zachary Zemmel, Christopher A. Walsh
Summary: MIPP-Seq is an ultra-sensitive, low-cost mosaic mutation detection technology that effectively mitigates allelic dropout, amplification bias, and sequencing artifacts. By utilizing independent analyses of multiple reactions, MIPP-Seq can precisely quantify mutations at extremely low allelic fractions across multiple tissues and mutation categories, with broad potential for research and clinical applications.
BMC MEDICAL GENOMICS
(2021)
Article
Biology
Eirik Hoye, Vegar J. Dagenborg, Annette Torgunrud, Christin Lund-Andersen, Asmund A. Fretland, Susanne Lorenz, Bjrn Edwin, Eivind Hovig, Bastian Fromm, Else M. Inderberg, Victor Greiff, Anne H. Ree, Kjersti Flatmark
Summary: This study used T-cell receptor (TCR) repertoire sequencing to measure and characterize T-cell infiltration in colorectal liver metastasis (CLM). The results showed increased T-cell fractions in CLMs exposed to neoadjuvant chemotherapy (NACT) within a short interval prior to resection, and modestly increased clonality in NACT-exposed tumors regardless of the timing of NACT administration and surgery. Network analysis revealed that public clones contributed the majority of TCR sequence convergence.
Article
Gastroenterology & Hepatology
Nicholas van Buuren, Ricardo Ramirez, Cameron Soulette, Vithika Suri, Dong Han, Lindsey May, Scott Turner, P. C. Parvangada, Ross Martin, Henry L. Y. Chan, Patrick Marcellin, Maria Buti, Nam Bui, Neeru Bhardwaj, Anuj Gaggar, Li Li, Hongmei Mo, Becket Feierbach
Summary: The study utilized targeted long-read sequencing to analyze HBV integration events in liver biopsies, revealing chromosomal translocation associated with HBV integration. Long-read RNA sequencing allowed for accurate quantification of HBV transcriptome, with patients showing differences in transcription origin based on HBeAg status. The findings suggest a novel mechanism with mutagenic potential that may contribute to HCC progression.
Article
Immunology
Yanyu Ren, Runrong Li, Hanxiao Feng, Jieying Xie, Lin Gao, Shuai Chu, Yan Li, Fanliang Meng, Yunshan Ning
Summary: This study characterizes the immune environment in tumor progression of relapsed chemo-resistant ovarian cancer patients at single-cell resolution. The immunosuppressive microenvironment in ascites, including myeloid and gamma delta T cells, as well as peripheral CD8(+) T cells with chemotherapy-induced senescence/exhaustion, play important roles in recurrence and chemoresistance. TCR/BCR sequencing demonstrates the conservation of TCR clonal expansion in hyper-expanded CD8(+) T cells and extensive BCR clonal expansion without usage bias of V(D)J genes after chemotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jiayu Zhang, Tong Lu, Shiqi Lu, Shuaijun Ma, Donghui Han, Keying Zhang, Chao Xu, Shaojie Liu, Lunbiao Gan, Xinjie Wu, Fa Yang, Weihong Wen, Weijun Qin
Summary: Endothelial cells (ECs) have a crucial role in tumor progression, and anti-angiogenic therapy targeting the vascular endothelial growth factor (VEGF) pathway has limitations. Single-cell RNA sequencing data from various cancer types revealed tumor-specific tip-like ECs that promote tumor angiogenesis and inhibit anti-tumor immunity. Prostate-specific membrane antigen (PSMA) was identified as a specific marker for tip-like ECs, suggesting its potential as a target for non-prostate cancers' diagnosis and treatment.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Zihan Liu, Fuqiang Niu, Shaohua Yuan, Shuying Feng, Yanmei Li, Fengkun Lu, Tianbao Zhang, Jianfang Bai, Changping Zhao, Liping Zhang
Summary: This study investigated a new wheat thermo-sensitive cytoplasmic male sterility line, FA99, and found that its fertility conversion was mainly controlled by temperature, with the critical abortion period being the tetrad stage. Transcriptome analysis revealed significant changes in gene expression under different fertility environments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Jeffrey D. Krimmel-Morrison, Talayeh S. Ghezelayagh, Shenyi Lian, Yuezheng Zhang, Jeanne Fredrickson, Daniela Nachmanson, Kathryn T. Baker, Marc R. Radke, Enna Hun, Barbara M. Norquist, Mary J. Emond, Elizabeth M. Swisher, Rosa Ana Risques
GYNECOLOGIC ONCOLOGY
(2020)
Article
Multidisciplinary Sciences
Charles C. Valentine, Robert R. Young, Mark R. Fielden, Rohan Kulkarni, Lindsey N. Williams, Tan Li, Sheroy Minocherhomji, Jesse J. Salk
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Yuezheng Zhang, Brendan F. Kohrn, Ming Yang, Daniela Nachmanson, T. Rinda Soong, I-Hsiu Lee, Yong Tao, Hans Clevers, Elizabeth M. Swisher, Teresa A. Brentnall, Lawrence A. Loeb, Scott R. Kennedy, Jesse J. Salk, Kamila Naxerova, Rosa Ana Risques
Summary: PolyG-DS is a method that combines duplex sequencing and CRISPR-Cas9 technology for accurate, reproducible, and highly sensitive genotyping of PolyG repeat regions. It has been shown to have wide applications in tumor evolution, disease lineage tracing, and more.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Yoon Young Choi, Su-Jin Shin, Jae Eun Lee, Lisa Madlensky, Seung-Tae Lee, Ji Soo Park, Jeong-Hyeon Jo, Hyunki Kim, Daniela Nachmanson, Xiaojun Xu, Sung Hoon Noh, Jae-Ho Cheong, Olivier Harismendy
Summary: In a study of 71 patients with multiple primary cancers (MPCs), pathogenic variants affecting Lynch Syndrome (LS) genes were observed in a subset of patients. Additionally, loss of function variants in RECQL5 were found to be more prevalent in non-LS MPC patients. This suggests that genetic screening should be considered for synchronous cancers and metachronous MPCs, particularly in early-onset cases.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
J. Silvio Gutkind, Alfredo A. Molinolo, Xingyu Wu, Zhiyong Wang, Daniela Nachmanson, Olivier Harismendy, Ludmil B. Alexandrov, Beverly R. Wuertz, Frank G. Ondrey, Denise Laronde, Leigha D. Rock, Miriam Rosin, Charles Coffey, Valerie D. Butler, Lisa Bengtson, Chiu-Hsieh Hsu, Julie E. Bauman, Stephen M. Hewitt, Ezra Ew Cohen, H-H Sherry Chow, Scott M. Lippman, Eva Szabo
Summary: This study aimed to evaluate the potential role of metformin in oral premalignant lesions, showing that metformin can induce encouraging histological responses and modulation of the mTOR signaling pathway, although the clinical response rate was lower than expected.
Article
Oncology
Daniela Nachmanson, Adam Officer, Hidetoshi Mori, Jonathan Gordon, Mark F. Evans, Joseph Steward, Huazhen Yao, Thomas O'Keefe, Farnaz Hasteh, Gary S. Stein, Kristen Jepsen, Donald L. Weaver, Gillian L. Hirst, Brian L. Sprague, Laura J. Esserman, Alexander D. Borowsky, Janet L. Stein, Olivier Harismendy
Summary: The progression of Breast Ductal Carcinoma In Situ (DCIS) is influenced by microenvironmental and molecular factors, which are not well understood. This study analyzed multiple microdissected regions from 39 cases and characterized the mutational, transcriptional, histological, and microenvironmental landscape. Genetic divergence increased with physical distance and phenotypic and subtype heterogeneity was associated with underlying genetic heterogeneity. The study also identified an immune escape state with histological and molecular features located preferentially at DCIS regions.
Article
Cell Biology
Qiang Zhang, Dimitrios-Ilias Balourdas, Bruno Baron, Alon Senitzki, Tali E. Haran, Klas G. Wiman, Thierry Soussi, Andreas C. Joerger
Summary: The extremophile Alvinella pompejana, an annelid worm living near hydrothermal vents in the Pacific Ocean, has a p53 family gene with a highly thermostable DNA-binding domain, which may play a crucial role in maintaining genome integrity.
CELL DEATH & DISEASE
(2022)
Article
Biotechnology & Applied Microbiology
Danielle P. M. LeBlanc, Matthew Meier, Fang Yin Lo, Elizabeth Schmidt, Charles Valentine, Andrew Williams, Jesse J. Salk, Carole L. Yauk, Francesco Marchetti
Summary: Exposure to environmental mutagens increases the risk of cancer and genetic disorders. Using Duplex Sequencing (DS) technology, this study analyzed mutation induction in the bone marrow of MutaMouse males exposed to benzo(a)pyrene (BaP). The results revealed a linear dose-related induction of mutations across all targets, with heterochromatic and intergenic regions exhibiting the highest mutation frequencies. The types of mutations enriched in BaP-exposed mice were consistent with the known etiology of BaP mutagenesis. Furthermore, DS showed a positive correlation with the gold-standard transgenic rodent gene mutation assay.
Review
Oncology
Thierry Soussi
Summary: With the advancement of genotyping technology, a large number of uncommon SNPs have been discovered, but many resources are biased towards European populations. TP53 gene is the most frequently mutated gene in human cancer, and its SNPs must be rigorously evaluated to avoid misclassifications. The recent discovery of numerous benign SNPs within the coding region of TP53 highlights the importance of including populations of different ethnic origins in genetic studies.
Article
Toxicology
Annette E. Dodge, Danielle P. M. LeBlanc, Gu Zhou, Andrew Williams, Matthew J. Meier, Phu Van, Fang Yin Lo, Charles C. Valentine, Jesse J. Salk, Carole L. Yauk, Francesco Marchetti
Summary: Duplex Sequencing (DS) is a high-accuracy DNA sequencing technology that has advantages over conventional mutagenicity assays. In this study, DS was used to analyze mutations induced by procarbazine (PRC) in mouse bone marrow. DS detected significant increases in mutation frequencies and changes to mutation spectra at different PRC doses, demonstrating its superiority over classical mutagenicity assays.
ARCHIVES OF TOXICOLOGY
(2023)
Letter
Biochemistry & Molecular Biology
Thierry Soussi
HUMAN MOLECULAR GENETICS
(2023)
Meeting Abstract
Oncology
Daniela Nachmanson, Mark F. Evans, Joseph Steward, Adam Officer, Huazhen Yao, Thomas J. O'Keefe, Farnaz Hasteh, Gary S. Stein, Kristen Jepsen, Donald L. Weaver, Gillian L. Hirst, Brian L. Sprague, Laura J. Esserman, Alexander Borowsky, Janet L. Stein, Olivier Harismendy
Meeting Abstract
Environmental Sciences
K. Tanis, P. A. Escobar, D. Nachmanson, B. Grasl-Kraupp, C. C. Valentine, J. Salk
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2021)
Meeting Abstract
Oncology
Olivier Harismendy, Daniela Nachmanson, Mark F. Evans, Hidetoshi Mori, Adam Officer, Christina Yau, Joseph Steward, Huazhen Yao, Thomas O'Keefe, Farnaz Hasteh, Gary S. Stein, Kristen Jepsen, Michael Campbell, Donald L. Weaver, Gillian L. Hirst, Brian L. Sprague, Laura J. Esserman, Jonathan A. Gordon, Alexander Borowsky, Janet L. Stein
Meeting Abstract
Oncology
Jeffrey D. Krimmel-Morrison, Shenyi Lian, Yuezheng Zhang, Jeanne Fredrickson, Daniela Nachmanson, Kathryn T. Baker, Marc R. Radke, Enna Hun, Barbara Norquist, Mary J. Emond, Elizabeth M. Swisher, Rosa Ana Risques
CLINICAL CANCER RESEARCH
(2020)