Mutation spectrums of TSC1 and TSC2 in Chinese women with lymphangioleiomyomatosis (LAM)
Autoři:
Jie Liu aff001; Weiwei Zhao aff005; Xiaohua Ou aff006; Zhen Zhao aff006; Changming Hu aff006; Mingming Sun aff006; Feifei Liu aff006; Junhao Deng aff006; Weili Gu aff001; Jiaying An aff002; Qingling Zhang aff001; Xiaoxian Zhang aff001; Jiaxing Xie aff001; Shiyue Li aff001; Rongchang Chen aff009; Shihui Yu aff005; Nanshan Zhong aff001
Působiště autorů:
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
aff001; Guangzhou Institute for Respiratory Health, Guangzhou, Guangdong, China
aff002; State Key Laboratory of Respiratory Diseases, Guangzhou, Guangdong, China
aff003; National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong, China
aff004; Guangzhou KingMed Diagnostics Group Co., Ltd, Guangzhou, Guangdong, China
aff005; Clinical Genome Center, KingMed Center for Clinical Laboratory Co., Ltd, Guangzhou, Guangdong, China
aff006; KingMed College of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China
aff007; Guangzhou KingMed Translational Medicine Institute Co., Ltd, Guangzhou, Guangdong, China
aff008; Department of Pulmonary and Critical Care Medicine, Shenzhen People's Hospital, Shenzhen, Guangdong, China
aff009; KingMed JianShi Innovation Institute (Guangzhou) Co., Ltd, Guangzhou, Guangdong, China
aff010
Vyšlo v časopise:
PLoS ONE 14(12)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0226400
Souhrn
The aim of our study was to elucidate the landscapes of genetic alterations of TSC1 and TSC2 as well as other possible non-TSC1/2 in Lymphangioleiomyomatosis (LAM) patients. Sixty-one Chinese LAM patients’ clinical information was collected. Tumor biopsies and matched leukocytes from these patients were retrospectively analyzed by next generation sequencing (NGS), chromosomal microarray analysis (CMA), and multiplex ligation-dependent probe amplification (MLPA). Eighty-six TSC1/2 variants were identified in 46 of the 61 LAM patients (75.4%) in which TSC2 and TSC1 variants were 88.37% and 11.63% respectively. The 86 variants are composed of (i) 52 single nucleotide variants (SNVs) (including 30 novel variants), (ii) 23 indels (including 21deletions, and 2 insertions), (iii) a germline duplication of exon 31–42 of TSC2, (iv) a 2.68 Mb somatic duplication containing TSC2, and (v) 9 regions with copy-neutral loss of heterogeneity (CN-LOHs) present only in the LAM patients with single TSC1/2 mutations. Sixty-one non-TSC1/2 variants in 31 genes were identified in 37 LAM patients. Combined applications of different techniques are necessary to achieve maximal detection rate of TSC1/2 variants in LAM patients. Thirty novel TSC1/2 variants expands the spectrum of TSC1/2 in LAM patients. Identification of 61 non-TSC1/2 variants suggests that alternative genes might have contributed to the initiation and progression of LAM.
Klíčová slova:
Human genetics – Carcinogenesis – Mutation databases – Nonsense mutation – Mutation detection – Biopsy – Somatic mutation – Germline mutation
Zdroje
1. McCormack FX, Gupta N, Finlay GR, Young LR, Taveira-DaSilva AM, Glasgow CG, et al. (2016) Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management. American journal of respiratory and critical care medicine 194 (6): 748–761. doi: 10.1164/rccm.201607-1384ST 27628078
2. Taillé C, Borie R, Crestani B. (2011) Current management of lymphangioleiomyomatosis. Current opinion in pulmonary medicine 17 (5): 374–378. doi: 10.1097/MCP.0b013e328349ac8c 21760507
3. Harari S, Spagnolo P, Cocconcelli E, Luisi F, Cottin V. (2018) Recent advances in the pathobiology and clinical management of lymphangioleiomyomatosis. Current opinion in pulmonary medicine 24 (5): 469–476. doi: 10.1097/MCP.0000000000000502 29927757
4. Gupta N, Finlay GA, Kotloff RM, Strange C, Wilson KC, Young LR, et al. (2017) Lymphangioleiomyomatosis Diagnosis and Management: High-Resolution Chest Computed Tomography, Transbronchial Lung Biopsy, and Pleural Disease Management. An Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guideline. American journal of respiratory and critical care medicine 196 (10): 1337–1348. doi: 10.1164/rccm.201709-1965ST 29140122
5. Avila NA, Dwyer AJ, Rabel A, Moss J. (2007) Sporadic lymphangioleiomyomatosis and tuberous sclerosis complex with lymphangioleiomyomatosis: comparison of CT features. Radiology 242 (1): 277–285. doi: 10.1148/radiol.2421051767 17105849
6. Chang WY, Cane JL, Blakey JD, Kumaran M, Pointon KS, Johnson SR. (2012) Clinical utility of diagnostic guidelines and putative biomarkers in lymphangioleiomyomatosis. Respiratory research 13: 34. doi: 10.1186/1465-9921-13-34 22513045
7. Young LR, Inoue Y, McCormack FX. (2008) Diagnostic potential of serum VEGF-D for lymphangioleiomyomatosis. The New England journal of medicine 358 (2): 199–200. doi: 10.1056/NEJMc0707517 18184970
8. Hodges AK, Li S, Maynard J, Parry L, Braverman R, Cheadle JP, et al. (2001) Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin. Human molecular genetics 10 (25): 2899–2905. doi: 10.1093/hmg/10.25.2899 11741833
9. van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, et al. (1998) Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Human molecular genetics 7 (6): 1053–1057. doi: 10.1093/hmg/7.6.1053 9580671
10. Krencz I, Sebestyen A, Papay J, Jeney A, Hujber Z, Burger CD, et al. (2018) In situ analysis of mTORC1/2 and cellular metabolism-related proteins in human Lymphangioleiomyomatosis. Human pathology 79: 199–207. doi: 10.1016/j.humpath.2018.05.018 29885404
11. Tomlinson IP, Roylance R, Houlston RS. (2001) Two hits revisited again. Journal of medical genetics 38 (2): 81–85. doi: 10.1136/jmg.38.2.81 11158170
12. Knudson AG. (1996) Hereditary cancer: two hits revisited. Journal of cancer research and clinical oncology 122 (3): 135–140. doi: 10.1007/bf01366952 8601560
13. Muzykewicz DA, Sharma A, Muse V, Numis AL, Rajagopal J, Thiele EA. (2009) TSC1 and TSC2 mutations in patients with lymphangioleiomyomatosis and tuberous sclerosis complex. Journal of medical genetics 46 (7): 465–468. doi: 10.1136/jmg.2008.065342 19419980
14. Carsillo T, Astrinidis A, Henske EP. (2000) Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proceedings of the National Academy of Sciences of the United States of America 97 (11): 6085–6090. doi: 10.1073/pnas.97.11.6085 10823953
15. Feemster LC, Lyons PG, Chatterjee RS, Kidambi P, McCormack FX, Moss J, et al. (2017) Summary for Clinicians: Lymphangioleiomyomatosis Diagnosis and Management Clinical Practice Guideline. Annals of the American Thoracic Society 14 (7): 1073–1075. doi: 10.1513/AnnalsATS.201609-685CME 28665705
16. May T. (2015) On the justifiability of ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. The Journal of law, medicine & ethics: a journal of the American Society of Law, Medicine & Ethics 43 (1): 134–142.
17. Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, et al. (2013) ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genetics in medicine: official journal of the American College of Medical Genetics 15 (7): 565–574.
18. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in medicine: official journal of the American College of Medical Genetics 17 (5): 405–424.
19. Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. (2017) Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. The Journal of molecular diagnostics: JMD 19 (1): 4–23. doi: 10.1016/j.jmoldx.2016.10.002 27993330
20. Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT. (2011) LOVD v.2.0: the next generation in gene variant databases. Human mutation 32 (5): 557–563. doi: 10.1002/humu.21438 21520333
21. Wang JC, Ross L, Mahon LW, Owen R, Hemmat M, Wang BT, et al. (2015) Regions of homozygosity identified by oligonucleotide SNP arrays: evaluating the incidence and clinical utility. European journal of human genetics: EJHG 23 (5): 663–671. doi: 10.1038/ejhg.2014.153 25118026
22. Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST. (2011) American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genetics in medicine: official journal of the American College of Medical Genetics 13 (7): 680–685.
23. Krueger DA, Northrup H. (2013) Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatric neurology 49 (4): 255–265. doi: 10.1016/j.pediatrneurol.2013.08.002 24053983
24. Northrup H, Krueger DA. (2013) Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference. Pediatric neurology 49 (4): 243–254. doi: 10.1016/j.pediatrneurol.2013.08.001 24053982
25. Fujita A, Ando K, Kobayashi E, Mitani K, Okudera K, Nakashima M, et al. (2016) Detection of low-prevalence somatic TSC2 mutations in sporadic pulmonary lymphangioleiomyomatosis tissues by deep sequencing. Human genetics 135 (1): 61–68. doi: 10.1007/s00439-015-1611-0 26563443
26. Nellist M, Brouwer RW, Kockx CE, van Veghel-Plandsoen M, Withagen-Hermans C, Prins-Bakker L, et al. (2015) Targeted Next Generation Sequencing reveals previously unidentified TSC1 and TSC2 mutations. BMC medical genetics 16: 10. doi: 10.1186/s12881-015-0155-4 25927202
27. Tyburczy ME1, Dies KA2, Glass J3, Camposano S4, Chekaluk Y1, Thorner AR, et al. (2015) Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing. PLoS genetics 11 (11): e1005637. doi: 10.1371/journal.pgen.1005637 26540169
28. Badri KR, Gao L, Hyjek E, Schuger N, Schuger L, Qin W, et al. (2013) Exonic mutations of TSC2/TSC1 are common but not seen in all sporadic pulmonary lymphangioleiomyomatosis. American journal of respiratory and critical care medicine 187 (6): 663–665. doi: 10.1164/ajrccm.187.6.663 23504366
29. Lam HC, Nijmeh J, Henske EP. (2017) New developments in the genetics and pathogenesis of tumours in tuberous sclerosis complex. The Journal of pathology 241 (2): 219–225. doi: 10.1002/path.4827 27753446
30. Goncharova EA, Goncharov DA, Li H, Pimtong W, Lu S, Khavin I, et al. (2011) mTORC2 is required for proliferation and survival of TSC2-null cells. Molecular and cellular biology 31 (12): 2484–2498. doi: 10.1128/MCB.01061-10 21482669
31. Maze I, Noh K-M, Soshnev AA, Allis CD. (2014) Every amino acid matters: essential contributions of histone variants to mammalian development and disease. Nature reviews. Genetics 15 (4): 259–271. doi: 10.1038/nrg3673 24614311
32. Zhou J, Shrikhande G, Xu J, McKay RM, Burns DK, Johnson JE, et al. (2011) Tsc1 mutant neural stem/progenitor cells exhibit migration deficits and give rise to subependymal lesions in the lateral ventricle. Genes & development 25 (15): 1595–1600.
33. Martin KR, Zhou W, Bowman MJ, Shih J, Au KS, Dittenhafer-Reed KE, et al. (2017) The genomic landscape of tuberous sclerosis complex. Nature communications 8: 15816. doi: 10.1038/ncomms15816 28643795
34. Uhlmann EJ, Apicelli AJ, Baldwin RL, Burke SP, Bajenaru ML, Onda H, et al. (2002) Heterozygosity for the tuberous sclerosis complex (TSC) gene products results in increased astrocyte numbers and decreased p27-Kip1 expression in TSC2+/- cells. Oncogene 21 (25): 4050–4059. doi: 10.1038/sj.onc.1205435 12037687
35. Sato T, Seyama K, Fujii H, Maruyama H, Setoguchi Y, Iwakami S, et al. (2002) Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis. Journal of human genetics 47 (1): 20–28. doi: 10.1007/s10038-002-8651-8 11829138
36. Au KS, Rodriguez JA, Finch JL, Volcik KA, Roach ES, Delgado MR, et al. (1998) Germ-line mutational analysis of the TSC2 gene in 90 tuberous-sclerosis patients. American journal of human genetics 62 (2): 286–294. doi: 10.1086/301705 9463313
37. Morrison PJ. (2009) Tuberous sclerosis: epidemiology, genetics and progress towards treatment. Neuroepidemiology 33 (4): 342–343. doi: 10.1159/000254570 19887840
38. Urban T. (2000) Epidémiologie clinique et moléculaire de la lymphangioleiomyomatose et de l'atteinte pulmonaire de la sclérose tubéreuse. Revue des maladies respiratoires 17 (2 Pt 2): 597–603.
Článok vyšiel v časopise
PLOS One
2019 Číslo 12
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Masturbační chování žen v ČR − dotazníková studie
- Nejasný stín na plicích – kazuistika
- Těžké menstruační krvácení může značit poruchu krevní srážlivosti. Jaký management vyšetření a léčby je v takovém případě vhodný?
- Somatizace stresu – typické projevy a možnosti řešení
Najčítanejšie v tomto čísle
- Methylsulfonylmethane increases osteogenesis and regulates the mineralization of the matrix by transglutaminase 2 in SHED cells
- Oregano powder reduces Streptococcus and increases SCFA concentration in a mixed bacterial culture assay
- The characteristic of patulous eustachian tube patients diagnosed by the JOS diagnostic criteria
- Parametric CAD modeling for open source scientific hardware: Comparing OpenSCAD and FreeCAD Python scripts