Article
Multidisciplinary Sciences
N. Shukla, M. F. Levine, G. Gundem, D. Domenico, B. Spitzer, N. Bouvier, J. E. Arango-Ossa, D. Glodzik, J. S. Medina-Martinez, U. Bhanot, J. Gutierrez-Abril, Y. Zhou, E. Fiala, E. Stockfisch, S. Li, M. Rodriguez-Sanchez, T. O'Donohue, C. Cobbs, M. H. A. Roehrl, J. Benhamida, F. Iglesias Cardenas, M. Ortiz, M. Kinnaman, S. Roberts, M. Ladanyi, S. Modak, S. Farouk-Sait, E. Slotkin, M. A. Karajannis, F. Dela Cruz, J. Glade Bender, A. Zehir, A. Viale, M. F. Walsh, A. L. Kung, E. Papaemmanuil
Summary: The authors developed a workflow to deliver comprehensive cWGTS results within clinically-relevant timeframes. Compared to other diagnostic methods, cWGTS has the potential to capture all clinically reported mutations with comparable sensitivity. These findings provide important technical considerations for implementing cWGTS in clinical oncology.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Siwei Chen, Yuan Liu, Yingying Zhang, Shayne D. Wierbowski, Steven M. Lipkin, Xiaomu Wei, Haiyuan Yu
Summary: The study presents a computational framework that characterizes the functional relevance of mutational hotspots in the context of a human 3D interactome network. The analysis shows that hotspots are located in network hub proteins and are enriched on protein interaction interfaces. The framework enables systematic identification of specific protein interactions affected by hotspot mutations and reveals genome-wide relationships among hotspots.
Article
Biochemistry & Molecular Biology
Arsen Arakelyan, Ani Melkonyan, Siras Hakobyan, Uljana Boyarskih, Arman Simonyan, Lilit Nersisyan, Maria Nikoghosyan, Maxim Filipenko, Hans Binder
Summary: This study revealed significant differences in transcriptomic landscapes of breast and ovarian cancers associated with BRCA1 and BRCA2 mutations, indicating that these mutations affect different biological functions and have differential associations with phenotype characteristics and PARP-inhibitor gene signatures. Further investigations with larger groups of mutation carriers are needed to refine the understanding of the molecular mechanisms of breast and ovarian cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Amrit L. Pappula, Shayaan Rasheed, Golrokh Mirzaei, Ruben C. Petreaca, Renee A. Bouley
Summary: Glioma patients with IDH1 mutation show significant genetic differences compared to patients with wild-type IDH1, including co-mutations and gene expression levels, which may contribute to a better prognosis.
Review
Oncology
Michal Gola, Przemyslaw Stefaniak, Janusz Godlewski, Barbara Alicja Jereczek-Fossa, Anna Starzynska
Summary: POLD1, a subunit of DNA polymerase delta complex, is crucial for DNA replication and repair. Its mutations have been found in various malignancies and its expression patterns have been associated with clinicopathological features. This review aims to summarize the current knowledge and future prospects of POLD1 in cancer research.
Article
Biotechnology & Applied Microbiology
Tian-Jian Yu, Ding Ma, Ying-Ying Liu, Yi Xiao, Yue Gong, Yi-Zhou Jiang, Zhi-Ming Shao, Xin Hu, Gen-Hong Di
Summary: This study reveals the heterogeneity in energy metabolism of breast cancer through integrative analyses of multiple datasets. Energy-related metabolic signatures can stratify tumors into different prognostic clusters, reflecting the intertumoral metabolic heterogeneity. Furthermore, it is found that the metabolic status of malignant cells at single-cell resolution plays a significant role, while interactions with factors from the tumor microenvironment are unexpected.
Article
Multidisciplinary Sciences
Mingyi Yang, Omer Ali, Magnar Bjoras, Junbai Wang
Summary: In this article, a non-coding SNVs analysis tool called bpb3 is proposed to identify functional mutation blocks (FMBs) by integrating genome sequencing and transcriptome data. A two-level Bayesian approach with a biophysical model is implemented to compute TF-DNA binding affinity changes based on clustered position weight matrices (PWMs) from over 1700 TF-motifs. By testing datasets from follicular lymphoma and melanoma, bpb3 automatically and robustly identifies FMBs, providing insights into patho-mechanisms and therapeutic targets.
Article
Multidisciplinary Sciences
Diletta Fontana, Ilaria Crespiatico, Valentina Crippa, Federica Malighetti, Matteo Villa, Fabrizio Angaroni, Luca De Sano, Andrea Aroldi, Marco Antoniotti, Giulio Caravagna, Rocco Piazza, Alex Graudenzi, Luca Mologni, Daniele Ramazzotti
Summary: The authors develop a method, ASCETIC, to identify evolutionary signatures associated with different prognostic outcomes across different cancer types, using bulk and single-cell sequencing data.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Caitlyn Vlasschaert, Taralynn Mack, J. Brett Heimlich, Abhishek Niroula, Md Mesbah Uddin, Joshua Weinstock, Brian Sharber, Alexander J. Silver, Yaomin Xu, Michael Savona, Christopher Gibson, Matthew B. Lanktree, Michael J. Rauh, Benjamin L. Ebert, Pradeep Natarajan, Siddhartha Jaiswal, Alexander G. Bick
Summary: Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related somatic mosaicism associated with significant morbidity and mortality. Differentiating true CHIP mutations from sequencing artifacts and germ line variants is a bioinformatic challenge. We present a stepwise method to improve the accuracy of CHIP calls using filtering, variant annotation, and population-based associations. This high-fidelity call set refines population-based associations of CHIP with incident outcomes and is crucial for clinical diagnostic assays.
Article
Genetics & Heredity
Shadi Darvish Shafighi, Szymon M. Kielbasa, Julieta Sepulveda-Yanez, Ramin Monajemi, Davy Cats, Hailiang Mei, Roberta Menafra, Susan Kloet, Hendrik Veelken, Cornelis A. M. van Bergen, Ewa Szczurek
Summary: CACTUS is a probabilistic model that integrates whole exome, single-cell RNA, and B cell receptor sequencing data to map single cells to imperfect genotypes of tumor clones. The integration of independent measurements increases model certainty and improves performance in drawing genotype-to-phenotype maps in tumors.
Article
Cell Biology
Ying Jiang, Baotong Zheng, Yang Yang, Xiangmei Li, Junwei Han
Summary: This study developed a software package SMDIC for the automated identification of immune cells driven by specific somatic mutations, providing a novel pipeline to discover mutation-specific immune cells and contribute to understanding the mechanisms underlying anticancer immune response.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Zhongshan Cheng, Michael Vermeulen, Micheal Rollins-Green, Brian DeVeale, Tomas Babak
Summary: Through integrating whole-genome sequencing and genetic data, a study identified 320 somatic non-coding mutations affecting gene expression, clustering into 47 cis-regulatory elements with diverse molecular mechanisms. These mutations exhibit hallmark features of non-coding drivers, preferentially disrupting transcription factor binding motifs, and being associated with a selective advantage, increased oncogene expression, and decreased tumor suppressor expression.
Article
Oncology
Minghan Jia, Ning Liao, Bo Chen, Guochun Zhang, Yulei Wang, Xuerui Li, Li Cao, Hsiaopei Mok, Chongyang Ren, Kai Li, Cheukfai Li, Lingzhu Wen, Jiali Lin, Guangnan Wei, Charles M. Balch
Summary: PIK3CA alterations are prevalent in Chinese breast cancer patients with different molecular features compared to Caucasians. These findings provide valuable insights for the application of PIK3CA inhibitors in Chinese patients.
Article
Multidisciplinary Sciences
Shizhe Yu, Haoren Wang, Lingpeng Yang, Yingxue Yan, Qiang Cai, Duo Ma, Long Jiang, Zehai Gao, Zhiyong Yu, Zongping Xia
Summary: The comprehensive study of the spatial-cellular anatomy of the human liver is crucial for understanding the cellular origins of liver disease. In this study, spatial transcriptomics were conducted on normal human liver tissue sections, providing detailed transcriptional information on liver zonation. A total of 6581 high-quality spots from normal livers were analyzed, mainly consisting of hepatocytes, which were classified into four sub-groups. These data serve as a reliable reference for studying the spatial heterogeneity of liver lobules.
Article
Biochemical Research Methods
Oliver Ocsenas, Juri Reimand
Summary: Somatic mutations in cancer genomes are associated with DNA replication timing and chromatin accessibility. This study uses machine learning to model mutation burden in cancer genomes and finds that the epigenomes of primary cancers are the strongest predictors of mutation burden. The genomic distributions of mutational signatures are also influenced by the epigenomes of matched cancer and tissue types. This study highlights the association of regional mutational processes with the epigenomes of primary cancers.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Denise Drongitis, Marianna Caterino, Lucia Verrillo, Pamela Santonicola, Michele Costanzo, Loredana Poeta, Benedetta Attianese, Adriano Barra, Gaetano Terrone, Maria Brigida Lioi, Simona Paladino, Elia Di Schiavi, Valerio Costa, Margherita Ruoppolo, Maria Giuseppina Miano
Summary: This study investigated the effects of mutations in the ARX gene on brain development and identified disrupted pathways related to cytoskeleton, protein synthesis, and splicing control. The study also found allele-dependent differences in neurite network organization, protein expression, and alternative splicing. Abnormal alternative splicing in the Neurexin-1 gene, which is involved in synaptic remodeling, was detected. These findings provide insights into the pathogenic mechanisms of ARX-related disorders and can inform the development of targeted therapies.
HUMAN MOLECULAR GENETICS
(2022)
Review
Biochemistry & Molecular Biology
Michele Spiniello, Mark Scalf, Amelia Casamassimi, Ciro Abbondanza, Lloyd M. Smith
Summary: RNA-binding proteins play a crucial role in the function of both coding and non-coding RNAs, and disruptions in RNA-protein interactions are associated with various pathological conditions. Different computational and experimental strategies have been developed to identify protein binders for specific RNA molecules. Among these, 'in cell' hybridization methods are considered the most reliable because they allow for the detection of proteins bound to specific RNAs in a cellular context.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Simona Cataldi, Marianna Aprile, Daniela Melillo, Ines Mucel, Sophie Giorgetti-Peraldi, Mireille Cormont, Paola Italiani, Matthias Blueher, Jean-Francois Tanti, Alfredo Ciccodicola, Valerio Costa
Summary: In this study, it was found that inflammatory factors secreted by metabolically-activated macrophages can modulate the expression and splicing of PPARG, leading to impaired adipocyte differentiation and exacerbating the defective PPAR gamma activity in hypertrophic adipose tissue.
Article
Oncology
Antonio Federico, Michele Fratello, Giovanni Scala, Lena Mobus, Alisa Pavel, Giusy del Giudice, Michele Ceccarelli, Valerio Costa, Alfredo Ciccodicola, Vittorio Fortino, Angela Serra, Dario Greco
Summary: The study found that current treatments for complex diseases have high toxicity and often lead to drug resistance, highlighting the need for novel and more specific pharmacological therapies. The authors developed an integrated network pharmacology framework combining mechanistic and chemocentric approaches to predict potential drug combinations for cancer therapy. The results show paclitaxel as a suitable drug for combination therapy in many cancer types and identified several non-cancer-related genes as potential candidates for cancer pharmacological treatment.
Article
Biochemistry & Molecular Biology
Gianluca Fasciolo, Gaetana Napolitano, Marianna Aprile, Simona Cataldi, Valerio Costa, Alfredo Ciccodicola, Sergio Di Meo, Paola Venditti
Summary: This study investigates the mechanism of insulin resistance caused by excess thyroid hormones and suggests that oxidative stress and changes in related genes may play a role in the development of insulin resistance.
Review
Oncology
Marianna Aprile, Valerio Costa, Amelia Cimmino, George Adrian Calin
Summary: The view of long noncoding RNAs as nonfunctional garbage has been outdated, as evidence suggests their role as golden junk, particularly in precision oncology. They have potential use as diagnostic and/or prognostic biomarkers, and advancements in technology have made it easier to profile them in multiple tumors and large cohorts.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Simona Cataldi, Mariagiovanna Tramontano, Valerio Costa, Marianna Aprile, Alfredo Ciccodicola
Summary: The increasing prevalence of diabetes mellitus worldwide leads to a higher incidence of macro- and micro-vascular complications, including diabetic retinopathy (DR), which is the leading cause of blindness in older diabetic patients. Chronic hyperglycemia is the main factor causing damage to retinal cells. Oxidative stress, inflammatory factors, and vascular endothelial growth factor signaling have been identified as contributors to the onset and progression of DR. Emerging evidence also suggests the involvement of non-coding RNA, particularly long non-coding RNAs (lncRNAs), in DR pathogenesis.
Review
Oncology
Cristina Pagano, Erika di Zazzo, Giorgio Avilia, Beatrice Savarese, Giovanna Navarra, Maria Chiara Proto, Donatella Fiore, Monica Rienzo, Patrizia Gazzerro, Chiara Laezza, Maurizio Bifulco
Summary: The epidemic spread of obesity is recognized as a global burden, and its link with cancer, known as adiponcosis, is of great interest in the scientific community. The mechanisms underlying adiponcosis, which may vary depending on cancer type, involve insulin resistance, chronic inflammation, and adipose tissue-derived hormones and cytokines. This review summarizes the current evidence on pathways, hormones, and interventions for obesity-related breast and colorectal cancers. It also discusses current targets and drugs for cancer treatment and potential therapeutic mechanisms.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Editorial Material
Endocrinology & Metabolism
Monica Rienzo, Cristina Pagano, Felice Crocetto, Erika Di Zazzo
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cell Biology
Simona Cataldi, Marianna Aprile, Caterina Perfetto, Brice Angot, Mireille Cormont, Alfredo Ciccodicola, Jean-Francois Tanti, Valerio Costa
Summary: Adipose tissue dysfunctions are associated with insulin resistance and type 2 diabetes mellitus. Targeting GIP receptor is a valid option for improving the efficacy of GLP-1 receptor agonists in diabetes treatment. However, the therapeutic potential and impact of targeting the GIP/GIPR axis on adipose tissue are controversial.
EUROPEAN JOURNAL OF CELL BIOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Amelia Casamassimi, Alfredo Ciccodicola, Monica Rienzo
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Erika Di Zazzo, Monica Rienzo, Amelia Casamassimi, Caterina De Rosa, Nicola Medici, Patrizia Gazzerro, Maurizio Bifulco, Ciro Abbondanza
Summary: PRDM1 and PRDM2 genes play important roles in T lymphocyte activation and differentiation. This study reveals that the expression of different transcripts of PRDM1 and PRDM2 changes during T lymphocyte activation, and is regulated by signaling pathways such as MAPK and PI3K. These transcripts have significant effects on the expression of key transcription factors involved in T lymphocyte differentiation.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Medicine, General & Internal
Felice Crocetto, Biagio Barone, Giulio D'Aguanno, Alfonso Falcone, Rosamaria de Vivo, Monica Rienzo, Laura Recchia, Erika Di Zazzo
Summary: Prostate cancer is a common cancer in men and a leading cause of death. Recent studies suggest that vitamin D supplementation does not have an impact on prostate health. Further research is needed to confirm this finding.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Gianluca Fasciolo, Gaetana Napolitano, Marianna Aprile, Simona Cataldi, Valerio Costa, Maria Teresa Muscari Tomajoli, Assunta Lombardi, Sergio Di Meo, Paola Venditti
Summary: This study aims to explore the correlation between oxidative stress and insulin resistance (IR) in skeletal muscle, using hyperthyroid rats as a model. The results suggest that hyperthyroidism-induced oxidative stress plays a role in the development of IR in muscle, and vitamin E supplementation can mitigate the effects of oxidative stress on IR.