-
1دورية أكاديمية
المؤلفون: Zhiwei Liu, Yang Luo, Samuel Kirimunda, Murielle Verboom, Olusegun O. Onabajo, Mateus H. Gouveia, Martin D. Ogwang, Patrick Kerchan, Steven J. Reynolds, Constance N. Tenge, Pamela A. Were, Robert T. Kuremu, Walter N. Wekesa, Nestory Masalu, Esther Kawira, Tobias Kinyera, Isaac Otim, Ismail D. Legason, Hadijah Nabalende, Herry Dhudha, Leona W. Ayers, Kishor Bhatia, James J. Goedert, Nathan Cole, Wen Luo, Jia Liu, Michelle Manning, Belynda Hicks, Ludmila Prokunina-Olsson, George Chagaluka, W. Thomas Johnston, Nora Mutalima, Eric Borgstein, George N. Liomba, Steve Kamiza, Nyengo Mkandawire, Collins Mitambo, Elizabeth M. Molyneux, Robert Newton, Ann W. Hsing, James E. Mensah, Anthony A. Adjei, Amy Hutchinson, Mary Carrington, Meredith Yeager, Rainer Blasczyk, Stephen J. Chanock, Soumya Raychaudhuri, Sam M. Mbulaiteye
المصدر: Communications Biology, Vol 7, Iss 1, Pp 1-9 (2024)
مصطلحات موضوعية: Biology (General), QH301-705.5
الوصف: Abstract Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10−6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10−8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10−6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2399-3642Test
-
2دورية أكاديمية
المؤلفون: Weiyin Zhou, Anja Fischer, Martin D. Ogwang, Wen Luo, Patrick Kerchan, Steven J. Reynolds, Constance N. Tenge, Pamela A. Were, Robert T. Kuremu, Walter N. Wekesa, Nestory Masalu, Esther Kawira, Tobias Kinyera, Isaac Otim, Ismail D. Legason, Hadijah Nabalende, Leona W. Ayers, Kishor Bhatia, James J. Goedert, Mateus H. Gouveia, Nathan Cole, Belynda Hicks, Kristine Jones, Michael Hummel, Mathias Schlesner, George Chagaluka, Nora Mutalima, Eric Borgstein, George N. Liomba, Steve Kamiza, Nyengo Mkandawire, Collins Mitambo, Elizabeth M. Molyneux, Robert Newton, Selina Glaser, Helene Kretzmer, Michelle Manning, Amy Hutchinson, Ann W. Hsing, Yao Tettey, Andrew A. Adjei, Stephen J. Chanock, Reiner Siebert, Meredith Yeager, Ludmila Prokunina-Olsson, Mitchell J. Machiela, Sam M. Mbulaiteye
المصدر: Nature Communications, Vol 14, Iss 1, Pp 1-13 (2023)
مصطلحات موضوعية: Science
الوصف: Abstract In high-income countries, mosaic chromosomal alterations in peripheral blood leukocytes are associated with an elevated risk of adverse health outcomes, including hematologic malignancies. We investigate mosaic chromosomal alterations in sub-Saharan Africa among 931 children with Burkitt lymphoma, an aggressive lymphoma commonly characterized by immunoglobulin-MYC chromosomal rearrangements, 3822 Burkitt lymphoma-free children, and 674 cancer-free men from Ghana. We find autosomal and X chromosome mosaic chromosomal alterations in 3.4% and 1.7% of Burkitt lymphoma-free children, and 8.4% and 3.7% of children with Burkitt lymphoma (P-values = 5.7×10−11 and 3.74×10−2, respectively). Autosomal mosaic chromosomal alterations are detected in 14.0% of Ghanaian men and increase with age. Mosaic chromosomal alterations in Burkitt lymphoma cases include gains on chromosomes 1q and 8, the latter spanning MYC, while mosaic chromosomal alterations in Burkitt lymphoma-free children include copy-neutral loss of heterozygosity on chromosomes 10, 14, and 16. Our results highlight mosaic chromosomal alterations in sub-Saharan African populations as a promising area of research.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2041-1723Test
-
3دورية أكاديمية
المؤلفون: Gabriel J Starrett, Kelly Yu, Yelena Golubeva, Petra Lenz, Mary L Piaskowski, David Petersen, Michael Dean, Ajay Israni, Brenda Y Hernandez, Thomas C Tucker, Iona Cheng, Lou Gonsalves, Cyllene R Morris, Shehnaz K Hussain, Charles F Lynch, Reuben S Harris, Ludmila Prokunina-Olsson, Paul S Meltzer, Christopher B Buck, Eric A Engels
المصدر: eLife, Vol 12 (2023)
مصطلحات موضوعية: polyomavirus, papillomavirus, bladder cancer, torque teno virus, solid organ transplant recipient, Medicine, Science, Biology (General), QH301-705.5
الوصف: A small percentage of bladder cancers in the general population have been found to harbor DNA viruses. In contrast, up to 25% of tumors of solid organ transplant recipients, who are at an increased risk of developing bladder cancer and have an overall poorer outcomes, harbor BK polyomavirus (BKPyV). To better understand the biology of the tumors and the mechanisms of carcinogenesis from potential oncoviruses, we performed whole genome and transcriptome sequencing on bladder cancer specimens from 43 transplant patients. Nearly half of the tumors from this patient population contained viral sequences. The most common were from BKPyV (N=9, 21%), JC polyomavirus (N=7, 16%), carcinogenic human papillomaviruses (N=3, 7%), and torque teno viruses (N=5, 12%). Immunohistochemistry revealed variable Large T antigen expression in BKPyV-positive tumors ranging from 100% positive staining of tumor tissue to less than 1%. In most cases of BKPyV-positive tumors, the viral genome appeared to be clonally integrated into the host chromosome consistent with microhomology-mediated end joining and coincided with focal amplifications of the tumor genome similar to other virus-mediated cancers. Significant changes in host gene expression consistent with the functions of BKPyV Large T antigen were also observed in these tumors. Lastly, we identified four mutation signatures in our cases, with those attributable to APOBEC3 and SBS5 being the most abundant. Mutation signatures associated with an antiviral drug, ganciclovir, and aristolochic acid, a nephrotoxic compound found in some herbal medicines, were also observed. The results suggest multiple pathways to carcinogenesis in solid organ transplant recipients with a large fraction being virus-associated.
وصف الملف: electronic resource
-
4دورية أكاديمية
المؤلفون: A. Rouf Banday, Olusegun O. Onabajo, Seraph Han-Yin Lin, Adeola Obajemu, Joselin M. Vargas, Krista A. Delviks-Frankenberry, Philippe Lamy, Ariunaa Bayanjargal, Clara Zettelmeyer, Oscar Florez-Vargas, Vinay K. Pathak, Lars Dyrskjøt, Ludmila Prokunina-Olsson
المصدر: Communications Biology, Vol 4, Iss 1, Pp 1-16 (2021)
مصطلحات موضوعية: Biology (General), QH301-705.5
الوصف: A. Rouf Banday et al. report targeting alternative splicing of APOBEC3B as a strategy to modulate APOBEC-mediated mutagenesis in cancers. Higher expression of the mutagenic APOBEC3B isoform predicted shorter progression-free survival in bladder cancer patients. Expression of this mutagenic isoform could be decreased by inducing skipping of APOBEC3B exon 5 in cells treated with SF3B1 inhibitor or splice-switching oligos.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2399-3642Test
-
5دورية أكاديمية
المؤلفون: Bin Zhu, Lijin Joo, Tongwu Zhang, Hela Koka, DongHyuk Lee, Jianxin Shi, Priscilla Lee, Difei Wang, Feng Wang, Wing-cheong Chan, Sze Hong Law, Yee-kei Tsoi, Gary M. Tse, Shui Wun Lai, Cherry Wu, Shuyuan Yang, Emily Ying Yang Chan, Samuel Yeung Shan Wong, Mingyi Wang, Lei Song, Kristine Jones, Amy Hutchinson, Belynda Hicks, Ludmila Prokunina-Olsson, Montserrat Garcia-Closas, Stephen Chanock, Lap Ah Tse, Xiaohong R. Yang
المصدر: HGG Advances, Vol 3, Iss 1, Pp 100076- (2022)
مصطلحات موضوعية: breast cancer, cancer genomics, Asian, driver gene selection pressure, mutational signatures, Genetics, QH426-470
الوصف: Summary: Recent genomic studies suggest that Asian breast cancer (BC) may have distinct somatic features; however, most comparisons of BC genomic features across populations did not account for differences in age, subtype, and sequencing methods. In this study, we analyzed whole-exome sequencing (WES) data to characterize somatic copy number alterations (SCNAs) and mutation profiles in 98 Hong Kong BC (HKBC) patients and compared with those from The Cancer Genome Atlas of European ancestry (TCGA-EA, N = 686), which had similar distributions of age at diagnosis and PAM50 subtypes as in HKBC. We developed a two-sample Poisson model to compare driver gene selection pressure, which reflects the effect sizes of cancer driver genes, while accounting for differences in sample size, sequencing platforms, depths, and mutation calling methods. We found that somatic mutation and SCNA profiles were overall very similar between HKBC and TCGA-EA. The selection pressure for small insertions and deletions (indels) in GATA3 (false discovery rate (FDR) corrected p < 0.01) and single-nucleotide variants (SNVs) in TP53 (nominal p = 0.02, FDR corrected p = 0.28) was lower in HKBC than in TCGA-EA. Among the 13 signatures of single-base substitutions (SBS) that are common in BC, we found a suggestively higher contribution of SBS18 and a lower contribution of SBS1 in HKBC than in TCGA-EA, while the two APOBEC-induced signatures showed similar prevalence. Our results suggest that the genomic landscape of BC was largely very similar between HKBC and TCGA-EA, despite suggestive differences in some driver genes and mutational signatures that warrant future investigations in large and diverse Asian populations.
وصف الملف: electronic resource
العلاقة: http://www.sciencedirect.com/science/article/pii/S2666247721000579Test; https://doaj.org/toc/2666-2477Test
-
6دورية أكاديمية
المؤلفون: Bin Zhu, Lap Ah Tse, Difei Wang, Hela Koka, Tongwu Zhang, Mustapha Abubakar, Priscilla Lee, Feng Wang, Cherry Wu, Koon Ho Tsang, Wing-cheong Chan, Sze Hong Law, Mengjie Li, Wentao Li, Suyang Wu, Zhiguang Liu, Bixia Huang, Han Zhang, Eric Tang, Zhengyan Kan, Soohyeon Lee, Yeon Hee Park, Seok Jin Nam, Mingyi Wang, Xuezheng Sun, Kristine Jones, Amy Hutchinson, Belynda Hicks, Ludmila Prokunina-Olsson, Jianxin Shi, Montserrat Garcia-Closas, Stephen Chanock, Xiaohong R. Yang
المصدر: Breast Cancer Research, Vol 21, Iss 1, Pp 1-11 (2019)
مصطلحات موضوعية: Tumor-infiltrating lymphocytes, Immune subtypes, Luminal breast cancer, Asian, Somatic mutations, APOBEC3B germline deletion, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Abstract Background Heterogeneity of immune gene expression patterns of luminal breast cancer (BC), which is clinically heterogeneous and overall considered as low immunogenic, has not been well studied especially in non-European populations. Here, we aimed at characterizing the immune gene expression profile of luminal BC in an Asian population and associating it with patient characteristics and tumor genomic features. Methods We performed immune gene expression profiling of tumor and adjacent normal tissue in 92 luminal BC patients from Hong Kong using RNA-sequencing data and used unsupervised consensus clustering to stratify tumors. We then used luminal patients from The Cancer Genome Atlas (TCGA, N = 564) and a Korean breast cancer study (KBC, N = 112) as replication datasets. Results Based on the expression of 130 immune-related genes, luminal tumors were stratified into three distinct immune subtypes. Tumors in one subtype showed higher level of tumor-infiltrating lymphocytes (TILs), characterized by T cell gene activation, higher expression of immune checkpoint genes, higher nonsynonymous mutation burden, and higher APOBEC-signature mutations, compared with other luminal tumors. The high-TIL subtype was also associated with lower ESR1/ESR2 expression ratio and increasing body mass index. The comparison of the immune profile in tumor and matched normal tissue suggested a tumor-derived activation of specific immune responses, which was only seen in high-TIL patients. Tumors in a second subtype were characterized by increased expression of interferon-stimulated genes and enrichment for TP53 somatic mutations. The presence of three immune subtypes within luminal BC was replicated in TCGA and KBC, although the pattern was more similar in Asian populations. The germline APOBEC3B deletion polymorphism, which is prevalent in East Asian populations and was previously linked to immune activation, was not associated with immune subtypes in our study. This result does not support the hypothesis that the germline APOBEC3B deletion polymorphism is the driving force for immune activation in breast tumors in Asian populations. Conclusion Our findings suggest that immune gene expression and associated genomic features could be useful to further stratify luminal BC beyond the current luminal A/B classification and a subset of luminal BC patients may benefit from checkpoint immunotherapy, at least in Asian populations.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/1465-542XTest
-
7دورية أكاديمية
المؤلفون: Olusegun O. Onabajo, Fang Wang, Mei-Hsuan Lee, Oscar Florez-Vargas, Adeola Obajemu, Chizu Tanikawa, Joselin M. Vargas, Shu-Fen Liao, Ci Song, Yu-Han Huang, Chen-Yang Shen, A. Rouf Banday, Thomas R. O’Brien, Zhibin Hu, Koichi Matsuda, Ludmila Prokunina-Olsson
المصدر: Frontiers in Immunology, Vol 12 (2021)
مصطلحات موضوعية: IFNL4, HCC (hepatocellular carcinoma), liver cirrhosis, ER stress, HCV (Hepatitis C), Immunologic diseases. Allergy, RC581-607
الوصف: IFNL3/IFNL4 polymorphisms are inversely associated with the risk of chronic hepatitis C virus (HCV) infection and cirrhosis, two major risk factors for developing hepatocellular carcinoma (HCC). To further explore these inverse associations and their molecular underpinnings, we analyzed IFNL3/IFNL4 polymorphisms represented by the IFNL4 genotype (presence of rs368234815-dG or rs12979860-T alleles) in HCV patients: 2969 from Japan and 2931 from Taiwan. IFNL4 genotype was associated with an increased risk of HCV-related HCC (OR=1.28, 95%CI=1.07-1.52, P=0.0058) in the general population of Japanese patients, but not in Taiwanese patients who achieved treatment-induced viral clearance. IFNL4 genotype was also associated with a decreased risk of cirrhosis (OR=0.66, 95%CI=0.46-0.93, P=0.018, in Taiwanese patients). We then engineered HepG2 cells to inducibly express IFN-λ4 in the presence or absence of interferon lambda receptor 1 (IFNLR1). Induction of IFN-λ4 resulted in its intracellular accumulation, mainly in lysosomes and late endosomes, and increased ER stress, leading to apoptosis and reduced proliferation. We identified the very-low-density lipoprotein receptor (VLDLR), which facilitates HCV entry into hepatocytes, as a transcript induced by IFN-λ4 but not IFN-λ3. Our results suggest that the molecular mechanisms underlying the anti-cirrhotic but pro-HCV associations observed for IFNL3/IFNL4 polymorphisms are, at least in part, contributed by intracellular accumulation of IFN-λ4 causing ER stress in hepatic cells.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2021.692263/fullTest; https://doaj.org/toc/1664-3224Test
-
8دورية أكاديمية
المؤلفون: Andriy Derkach, Isaac Otim, Ruth M. Pfeiffer, Olusegun O. Onabajo, Ismail D. Legason, Hadijah Nabalende, Martin D. Ogwang, Patrick Kerchan, Ambrose O. Talisuna, Leona W. Ayers, Steven J. Reynolds, Francis Nkrumah, Janet Neequaye, Kishor Bhatia, Thor G. Theander, Ludmila Prokunina-Olsson, Louise Turner, James J. Goedert, Thomas Lavstsen, Sam M. Mbulaiteye
المصدر: EBioMedicine, Vol 39, Iss , Pp 358-368 (2019)
مصطلحات موضوعية: Medicine, Medicine (General), R5-920
الوصف: Background: Endemic Burkitt lymphoma (eBL) is an aggressive childhood B-cell lymphoma linked to Plasmodium falciparum (Pf) malaria in sub-Saharan Africa. We investigated antibody reactivity to several human receptor-binding domains of the Pf erythrocyte membrane protein 1 (PfEMP1) that play a key role in malaria pathogenesis and are targets of acquired immunity to malaria. Methods: Serum/plasma IgG antibody reactivity was measured to 22 Pf antigens, including 18 to PfEMP1 CIDR domains between cases and controls from two populations (149 eBL cases and 150 controls from Ghana and 194 eBL cases and 600 controls from Uganda). Adjusted odds ratios (aORs) for case-control associations were estimated by logistic regression. Findings: There was stronger reactivity to the severe malaria associated CIDRα1 domains than other CIDR domains both in cases and controls. eBL cases reacted to fewer antigens than controls (Ghana: p = 0·001; Uganda: p = 0·03), with statistically significant lower ORs associated with reactivity to 13+ antigens in Ghana (aOR 0·39, 95% CI 0·24–0·63; pheterogeneity = 0·00011) and Uganda (aOR 0·60, 95% CI 0.41–0·88; pheterogeneity = 0·008). eBL was inversely associated with reactivity, coded as quartiles, to group A variant CIDRδ1 (ptrend = 0·035) in Ghana and group B CD36-binding variants CIDRα2·2 (ptrend = 0·006) and CIDRα2·4 (ptrend = 0·033) in Uganda, and positively associated with reactivity to SERA5 in Ghana (ptrend = 0·017) and Uganda (ptrend = 0·007) and group A CIDRα1·5 variant in Uganda only (ptrend = 0·034). Interpretation: eBL cases reacted to fewer antigens than controls using samples from two populations, Ghana and Uganda. Attenuated humoral immunity to Pf EMP1 may contribute to susceptibility to low-grade malaria and eBL risk. Funding: Intramural Research Program, National Cancer Institute and National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services. Keywords: Non-Hodgkin lymphoma, Plasmodium falciparum malaria, PfEMP1, Epstein-Barr virus, Burkitt lymphoma, Africa
وصف الملف: electronic resource
العلاقة: http://www.sciencedirect.com/science/article/pii/S2352396418305978Test; https://doaj.org/toc/2352-3964Test
-
9دورية أكاديمية
المؤلفون: Daniel Svensson, Matilda Rentoft, Anna M. Dahlin, Emma Lundholm, Pall I. Olason, Andreas Sjödin, Carin Nylander, Beatrice S. Melin, Johan Trygg, Erik Johansson, Ludmila Prokunina-Olsson
المصدر: PLoS ONE, Vol 15, Iss 9 (2020)
الوصف: The number of national reference populations that are whole-genome sequenced are rapidly increasing. Partly driving this development is the fact that genetic disease studies benefit from knowing the genetic variation typical for the geographical area of interest. A whole-genome sequenced Swedish national reference population (n = 1000) has been recently published but with few samples from northern Sweden. In the present study we have whole-genome sequenced a control population (n = 300) (ACpop) from Västerbotten County, a sparsely populated region in northern Sweden previously shown to be genetically different from southern Sweden. The aggregated variant frequencies within ACpop are publicly available (DOI 10.17044/NBIS/G000005) to function as a basic resource in clinical genetics and for genetic studies. Our analysis of ACpop, representing approximately 0.11% of the population in Västerbotten, indicates the presence of a genetic substructure within the county. Furthermore, a demographic analysis showed that the population from which samples were drawn was to a large extent geographically stationary, a finding that was corroborated in the genetic analysis down to the level of municipalities. Including ACpop in the reference population when imputing unknown variants in a Västerbotten cohort resulted in a strong increase in the number of high-confidence imputed variants (up to 81% for variants with minor allele frequency < 5%). ACpop was initially designed for cancer disease studies, but the genetic structure within the cohort will be of general interest for all genetic disease studies in northern Sweden.
وصف الملف: electronic resource
-
10دورية أكاديمية
المؤلفون: Thomas R O'Brien, Rune Hartmann, Ludmila Prokunina-Olsson
المصدر: eLife, Vol 8 (2019)
مصطلحات موضوعية: Hepatitis C, host-pathogen interactions, interferon-lambda 4, innate immunity, Medicine, Science, Biology (General), QH301-705.5
الوصف: Polymorphisms in the IFNL4 gene that affect both the presence and the form of the coded protein are associated with changes in the hepatitis C virus.
وصف الملف: electronic resource
النص الكامل