Article
Oncology
Tian-Gen Chang, Yingying Cao, Eldad D. Shulman, Uri Ben-David, Alejandro A. Schaffer, Eytan Ruppin
Summary: This study examined the ability of two common copy-number alteration (CNA) scores, AS and FGA, to predict survival following immunotherapy in 3139 patients with different cancer types. The results showed that AS and FGA could predict overall survival in both high-TMB and low-TMB patients, but their predictive power was limited to only a few specific cancer types. Larger sample sizes are needed to determine their clinical utility in other cancer types. Additionally, a simple elbow-point-based method was proposed to determine the cutoff for calling CNAs.
NPJ PRECISION ONCOLOGY
(2023)
Article
Oncology
Fumi Murakami, Yumi Tsuboi, Yuka Takahashi, Yoshiya Horimoto, Kaoru Mogushi, Takeshi Ito, Mitsuru Emi, Daisuke Matsubara, Tatsuhiro Shibata, Mitsue Saito, Yoshinori Murakami
Summary: Copy number variation (CNV) is a common polymorphism in the human genome, with somatic alterations at CNV sites detected in 39.9% of the CNV probes examined in invasive breast cancers. The most frequently altered regions included gains of 1q21-22, 8q21-24, 1q44, 3q11, and losses of 16q22-24. Gene ontology analysis revealed correlations between CNAs and transcription/RNA metabolism in relation to HER2 positivity and menopausal status in breast cancer patients.
Article
Biochemistry & Molecular Biology
Thomas F. Eleveld, Chaimaa Bakali, Paul P. Eijk, Phylicia Stathi, Lianne E. Vriend, Pino J. Poddighe, Bauke Ylstra
Summary: Large-scale chromosomal deletions are common in cancer and confer an oncogenic advantage, but the oncogenic drivers behind these deletions are difficult to identify. This study introduced a novel CRISPR-Cas9 technique to engineer large-scale deletions and create isogenic cell line models, successfully inducing deletions in neuroblastoma cell lines. The technique may provide valuable insights into the role of large-scale deletions in tumor development and growth.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Genetics & Heredity
Smruthy Sivakumar, F. Anthony San Lucas, Yasminka A. Jakubek, Zuhal Ozcan, Jerry Fowler, Paul Scheet
Summary: This study improves the sensitivity in identifying SCNAs by modeling B allele frequencies jointly and provides AI summaries for various tumor sites in TCGA. The research shows a high proportion of AI events and reveals recurrent events as well as previously uncharacterized patterns of cnLOH.
Article
Multidisciplinary Sciences
William N. William Jr, Xin Zhao, Joy J. Bianchi, Heather Y. Lin, Pan Cheng, J. Jack Lee, Hannah Carter, Ludmil B. Alexandrov, Jim P. Abraham, David B. Spetzler, Steven M. Dubinett, Don W. Cleveland, Webster Cavenee, Teresa Davoli, Scott M. Lippman
Summary: The research explores the impact of chromosomal dosage alterations in head and neck tumors, revealing a potential induction of immune heat response in precancer stages, while leading to immune suppression and depletion of cytotoxic cells in tumor progression. Loss of 9p21.3 and 9p arm-level decrease can disrupt immunity and affect tumor infiltration of cytotoxic cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Mate Naszai, Karen Bellec, Yachuan Yu, Alvaro Roman-Fernandez, Emma Sandilands, Joel Johansson, Andrew D. Campbell, Jim C. Norman, Owen J. Sansom, David M. Bryant, Julia B. Cordero
Summary: RAL GTPases activate EGFR/MAPK signaling in the intestine, impacting stem cell proliferation and tumorigenic growth, revealing their essential role in adult tissue homeostasis and malignant transformation.
Review
Genetics & Heredity
M. Felicia Basilicata, Claudia Isabelle Keller Valsecchi
Summary: Gene dosage changes play a significant role at the intersection of evolutionary advantage and pathogenicity, providing a common ground for understanding developmental disorders caused by copy number alterations.
Article
Oncology
Ming-Hung Shen, Chi-Jung Huang, Thien-Fiew Ho, Chih-Yi Liu, Ying-Yih Shih, Ching-Shui Huang, Chi-Cheng Huang
Summary: This study aims to enhance the prognostication of colorectal cancer by integrating SNP and GE microarrays and identifying genes with concurrent gains and losses to develop a prognostic signature. The results show that the colorectal cancer concurrent gene signature has the potential to predict recurrence, metastasis, or mortality among 1746 patients.
Article
Biology
Bryan D. Clifton, Imtiyaz Hariyani, Ashlyn Kimura, Fangning Luo, Alvin Nguyen, Jose M. Ranz
Summary: This study shows a positive correlation between Sdic copy number and total expression, and vast differences in mRNA abundance among paralogs in the testes of different strains. Moreover, expression differentiation of paralogs in meiotic cell types within the testes is revealed by single cell and nucleus RNA-sequencing data.
COMMUNICATIONS BIOLOGY
(2023)
Article
Genetics & Heredity
Amy B. Wilfert, Tychele N. Turner, Shwetha C. Murali, PingHsun Hsieh, Arvis Sulovari, Tianyun Wang, Bradley P. Coe, Hui Guo, Kendra Hoekzema, Trygve E. Bakken, Lara H. Winterkorn, Uday S. Evani, Marta Byrska-Bishop, Rachel K. Earl, Raphael A. Bernier, Michael C. Zody, Evan E. Eichler
Summary: Whole-genome sequencing data from 3,474 families revealed an excess of private, likely gene-disrupting variants in individuals with autism, which are under purifying selection. The study identified candidate genes not previously associated with autism and highlighted the importance of ultra-rare variants in autism risk. Private LGD variants were found to be significantly younger and act on a distinct set of genes, supporting a multi-hit model for autism.
Article
Neurosciences
Jennifer K. Forsyth, Eva Mennigen, Amy Lin, Daqiang Sun, Ariana Vajdi, Leila Kushan-Wells, Christopher R. K. Ching, Julio E. Villalon-Reina, Paul M. Thompson, Carrie E. Bearden
Summary: 22q11.2 deletion syndrome is associated with alterations in brain morphology, including reduced total surface area and increased cortical thickness in certain regions. Genes such as DGCR8, AIFM3, and P2RX6 play key roles in these cortical changes. The findings highlight the importance of integrating neuroanatomical and transcriptomic data to understand the molecular mechanisms underlying complex genetic disorders.
Article
Biochemical Research Methods
Yuqi Sheng, Ying Jiang, Yang Yang, Xiangmei Li, Jiayue Qiu, Jiashuo Wu, Liang Cheng, Junwei Han
Summary: Biological pathways are crucial in dictating disease states and drug responses, dysfunctional subpathways (SPs) have been associated with cancer, high-throughput sequencing allows for identification of dysfunctional SPs, a novel network-based method, CNA2Subpathway, integrates pathway topology information, multi-omics data, and SP crosstalk to identify cancer-relevant SPs driven by somatic CNAs. Validated in breast cancer and head and neck cancer datasets, CNA2Subpathway shows effectiveness in uncovering dysfunctional SPs associated with cancer immune response and patient prognosis.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Cell Biology
Pradeep Kumar Bhaskar, Sheryl Southard, Kelly Baxter, Mark Van Doren
Summary: This study reveals that JAK/STAT signaling promotes male development in germ cells by activating the chromatin reader Phf7, while this signaling pathway is blocked in XX (female) germ cells by the sex determination gene Sex lethal to maintain female development.
Article
Multidisciplinary Sciences
Pedro B. Pinto, Katrin Domsch, Xuefan Gao, Michaela Woelk, Julie Carnesecchi, Ingrid Lohmann
Summary: Hox proteins have similar binding specificities in vitro but control different morphologies in vivo. This paradox has been partially resolved with the discovery of low-affinity binding sites. The specificity of anterior Hox proteins, which are more promiscuous than posterior Hox proteins, is achieved through a precise balance of transcription factors and binding site affinities. Small variations in affinity change the enhancer's sensitivity to different Hox levels, resulting in perturbed gene expression and morphogenesis.
NATURE COMMUNICATIONS
(2022)
Article
Evolutionary Biology
Marc Krasovec, Remy Merret, Frederic Sanchez, Sophie Sanchez-Brosseau, Gwenael Piganeau
Summary: Through mutation accumulation experiments, we estimated the spontaneous chromosome duplication rates in six unicellular eukaryotic species, ranging from 1 x 10(-4) to 1 x 10(-3) per genome per generation. Chromosome duplication events can affect 1-7% of the total genome size. Our results support previous observations of chromosome-dependent dosage compensation effects, providing evidence that compensation occurs during translation.
GENOME BIOLOGY AND EVOLUTION
(2023)