Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation
Abstract Kidney transplantation is a lifesaving option for patients with end-stage kidney disease. In Taiwan, urothelial carcinoma (UC) is the most common de novo cancer after kidney transplantation (KT). UC has a greater degree of molecular heterogeneity than do other solid tumors. Few studies have...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03522-4 |
| _version_ | 1811287460143955968 |
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| author | Lee-Moay Lim Wen-Yu Chung Daw-Yang Hwang Chih-Chuan Yu Hung-Lung Ke Peir-In Liang Ting-Wei Lin Siao Muk Cheng A-Mei Huang Hung-Tien Kuo |
| author_facet | Lee-Moay Lim Wen-Yu Chung Daw-Yang Hwang Chih-Chuan Yu Hung-Lung Ke Peir-In Liang Ting-Wei Lin Siao Muk Cheng A-Mei Huang Hung-Tien Kuo |
| author_sort | Lee-Moay Lim |
| collection | DOAJ |
| description | Abstract Kidney transplantation is a lifesaving option for patients with end-stage kidney disease. In Taiwan, urothelial carcinoma (UC) is the most common de novo cancer after kidney transplantation (KT). UC has a greater degree of molecular heterogeneity than do other solid tumors. Few studies have explored genomic alterations in UC after KT. We performed whole-exome sequencing to compare the genetic alterations in UC developed after kidney transplantation (UCKT) and in UC in patients on hemodialysis (UCHD). After mapping and variant calling, 18,733 and 11,093 variants were identified in patients with UCKT and UCHD, respectively. We excluded known single-nucleotide polymorphisms (SNPs) and retained genes that were annotated in the Catalogue of Somatic Mutations in Cancer (COSMIC), in the Integrative Onco Genomic cancer mutations browser (IntOGen), and in the Cancer Genome Atlas (TCGA) database of genes associated with bladder cancer. A total of 14 UCKT-specific genes with SNPs identified in more than two patients were included in further analyses. The single-base substitution (SBS) profile and signatures showed a relative high T > A pattern compared to COMSIC UC mutations. Ingenuity pathway analysis was used to explore the connections among these genes. GNAQ, IKZF1, and NTRK3 were identified as potentially involved in the signaling network of UCKT. The genetic analysis of posttransplant malignancies may elucidate a fundamental aspect of the molecular pathogenesis of UCKT. |
| first_indexed | 2024-04-13T03:18:44Z |
| format | Article |
| id | doaj.art-ae7e7039684448ee8248bbf8416ab6da |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-13T03:18:44Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-ae7e7039684448ee8248bbf8416ab6da2022-12-22T03:04:50ZengBMCJournal of Translational Medicine1479-58762022-07-0120111410.1186/s12967-022-03522-4Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantationLee-Moay Lim0Wen-Yu Chung1Daw-Yang Hwang2Chih-Chuan Yu3Hung-Lung Ke4Peir-In Liang5Ting-Wei Lin6Siao Muk Cheng7A-Mei Huang8Hung-Tien Kuo9Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical UniversityDepartment of Computer Science and Information Engineering, National Kaohsiung University of Science and TechnologyNational Institute of Cancer Research, National Health Research InstituteNational Institute of Cancer Research, National Health Research InstituteDepartment of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDepartment of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical UniversityNational Institute of Cancer Research, National Health Research InstituteGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical UniversityDivision of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityAbstract Kidney transplantation is a lifesaving option for patients with end-stage kidney disease. In Taiwan, urothelial carcinoma (UC) is the most common de novo cancer after kidney transplantation (KT). UC has a greater degree of molecular heterogeneity than do other solid tumors. Few studies have explored genomic alterations in UC after KT. We performed whole-exome sequencing to compare the genetic alterations in UC developed after kidney transplantation (UCKT) and in UC in patients on hemodialysis (UCHD). After mapping and variant calling, 18,733 and 11,093 variants were identified in patients with UCKT and UCHD, respectively. We excluded known single-nucleotide polymorphisms (SNPs) and retained genes that were annotated in the Catalogue of Somatic Mutations in Cancer (COSMIC), in the Integrative Onco Genomic cancer mutations browser (IntOGen), and in the Cancer Genome Atlas (TCGA) database of genes associated with bladder cancer. A total of 14 UCKT-specific genes with SNPs identified in more than two patients were included in further analyses. The single-base substitution (SBS) profile and signatures showed a relative high T > A pattern compared to COMSIC UC mutations. Ingenuity pathway analysis was used to explore the connections among these genes. GNAQ, IKZF1, and NTRK3 were identified as potentially involved in the signaling network of UCKT. The genetic analysis of posttransplant malignancies may elucidate a fundamental aspect of the molecular pathogenesis of UCKT.https://doi.org/10.1186/s12967-022-03522-4Kidney transplantationMalignancyUrothelial carcinomaWhole exome sequencingMutations |
| spellingShingle | Lee-Moay Lim Wen-Yu Chung Daw-Yang Hwang Chih-Chuan Yu Hung-Lung Ke Peir-In Liang Ting-Wei Lin Siao Muk Cheng A-Mei Huang Hung-Tien Kuo Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation Journal of Translational Medicine Kidney transplantation Malignancy Urothelial carcinoma Whole exome sequencing Mutations |
| title | Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation |
| title_full | Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation |
| title_fullStr | Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation |
| title_full_unstemmed | Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation |
| title_short | Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation |
| title_sort | whole exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation |
| topic | Kidney transplantation Malignancy Urothelial carcinoma Whole exome sequencing Mutations |
| url | https://doi.org/10.1186/s12967-022-03522-4 |
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