Онкопедиатрия. 2017; 4: 283-289
Опухоль Вильмса: синдромальная и молекулярная диагностика
https://doi.org/10.15690/onco.v4i4.1814Аннотация
При опухоли Вильмса нередко выявляются генотипически-фенотипические корреляции. Детекция мутации по фенотипу дает возможность прогнозировать заболевание, индивидуализировать программу лечения с учетом всех рисков развития того или иного осложнения терапии. В статье представлены сведения об основных синдромах и генетически детерминированных заболеваниях, ассоциированных с развитием опухоли Вильмса. Высокий риск развития опухоли Вильмса (>20%) имеют пациенты с некоторыми WT1-ассоциированными синдромами (включая WAGR и Дениса–Драша), синдромом Перлмана, мозаичной перемежающейся анеуплоидией и анемией Фанкони с биаллельной BRCA2- мутацией. Умеренный риск развития нефробластомы (5–20%) отмечен в группах детей с синдромами Фрейзера, Беквита–Видемана, развившимися вследствие дисомии 11p15, и синдромом Симпсона–Голаби–Бемеля. К группе низкого риска развития нефробластомы (<5%) отнесены больные с изолированной гемигипертрофией, синдромами Блума и Ли–Фраумени, врожденным гиперпаратиреозом в сочетании с опухолями челюстей, нанизмом MULIBREY и различными хромосомными аберрациями. Развитие молекулярной биологии в будущем позволит разработать новые подходы к персонализированному лечению с добавлением в программы молекулярной таргетной терапии для пациентов с высоким риском рецидива заболевания.
Список литературы
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2. Wilms M. [Die Mischgeschwülste der Niere. In: Die Mischgeschwülste. (In German).] Leipzig: Verlag von Arthur Georgi; 1899.
3. Rivera MN, Haber DA. Wilms’ tumour: connecting tumorigenesis and organ development in the kidney. Nature Reviews Cancer. 2005;5(9):699–712. doi: 10.1038/nrc1696.
4. Breslow NE, Beckwith JB, Perlman EJ, Reeve AE. Age distributions, birth weights, nephrogenic rests, and heterogeneity in the pathogenesis of Wilms tumor. Pediatr Blood Cancer. 2006;47(3):260–267. doi: 10.1002/pbc.20891.
5. Stiller CA, Parkin DM. International variations in the incidence of childhood renal tumors. Br J Cancer. 1990;62(6):1026–1030. doi: 10.1038/bjc.1990.432.
6. Beckwith JB, Kiviat NB, Bonadio JF. Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms’ tumor. Pediatr Pathol. 1990;10(1–2):1–36. doi: 10.3109/15513819009067094.
7. Knudson AG. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971;68(4):820–823. doi: 10.1073/pnas.68.4.820.
8. Knudson AG, Jr., Strong LC. Mutation and cancer: a model for Wilms’ tumor of the kidney. J Natl Cancer Inst. 1972;48(2):313–324. doi: 10.1093/jnci/48.2.313.
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12. Rose EA, Glaser T, Jones C, et al. Complete physical map of the WAGR region of 11p13 localizes a candidate Wilms’ tumor gene. Cell. 1990;60(3):495–508. doi: 10.1016/0092-8674(90)90600-J.
13. Royer-Pokora B, Beier M, Henzler M, et al. Twenty-four new cases of WT1 germline mutations and review of the literature: genotype/phenotype correlations for Wilms tumor development. Am J Med Genet A. 2004;127A(3):249–257. doi: 10.1002/ajmg.a.30015.
14. Ruteshouser EC, Robinson SM, Huff V. Wilms tumor genetics: Mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors. Genes Chromosomes & Cancer. 2008;47(6):461–470. doi: 10.1002/gcc.20553.
15. Scott RH, Douglas J, Baskcomb L, et al. Constitutional 11p15 abnormalities, including heritable imprinting center mutations, cause nonsyndromic Wilms tumor. Nat Genet. 2008;40(11):1329–1334. doi: 10.1038/ng.243.
16. Baird PN, Santos A, Groves N, et al. Constitutional mutations in the WT1 gene in patients with Denys- Drash syndrome. Hum Mol Genet. 1992;1(5):301– 305. doi: 10.1093/hmg/1.5.301.
17. Barbaux S, Niaudet P, Gubler MC, et al. Donor splicesite mutations in WT1 are responsible for Frasier syndrome. Nat Genet. 1997;17(4):467–470. doi: 10.1038/ng1297-467.
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19. McDonald JM, Douglass EC, Fisher R, et al. Linkage of familial Wilms’ tumor predisposition to chromosome 19 and a two-locus model for the etiology of familial tumors. Cancer Res. 1998;58(7):1387–1390.
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23. DeBaun MR, Niemitz EL, McNeil DE, et al. Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects. Am J Hum Genet. 2002;70(3):604– 611. doi: 10.1086/338934.
24. Thavaraj V, Sethi A, Arya LS. Incomplete Beckwith-Wiedemann syndrome in a child with orbital rhabdomyosarcoma. Indian Pediatr. 2002;39(3):299–304.
25. Weksberg R, Nishikawa J, Caluseriu O, et al. Tumor development in the Beckwith- Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1. Hum Mol Genet. 2001;10(26):2989– 3000. doi: 10.1093/hmg/10.26.2989.
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28. Rahman N. Mechanisms predisposing to childhood overgrowth and cancer. Curr Opin Genet Dev. 2005;15(3):227–233. doi: 10.1016/j.gde.2005.04.007.
29. Pilia G, HughesBenzie RM, MacKenzie A, et al. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet. 1996;12(3):241–247. doi: 10.1038/ng0396-241.
30. Mariani S, Iughetti L, Bertorelli R, et al. Genotype/phenotype correlations of males affected by Simpson- Golabi-Behmel syndrome with GPC3 gene mutations: Patient report and review of the literature. J Pediatr Endocrinol Metab. 2003;16(2):225–232. doi: 10.1515/jpem.2003.16.2.225.
31. Green DM, Breslow NE, Beckwith JB, Norkool P. Screening of children with hemihypertrophy, aniridia, and Beckwith-Wiedemann syndrome in patients with Wilms tumor: a report from the National Wilms Tumor Study. Med Pediatr Oncol. 1993;21(3):188– 192. doi: 10.1002/mpo.2950210307.
32. Niemitz EL, Feinberg AP, Brandenburg SA, et al. Children with idiopathic hemihypertrophy and Beckwith-Wiedemann syndrome have different constitutional epigenotypes associated with Wilms tumor. Am J Hum Genet. 2005;77(5):887–891. doi: 10.1086/497540.
33. Henneveld HT, van Lingen RA, Hamel BCJ, et al. Perlman syndrome: four additional cases and review. Am J Med Genet. 1999;86(5):439–446. doi: 10.1002/(sici)1096- 8628(19991029)86:5<439::aidajmg9>3.0.co;2-4.
34. Perlman M, Goldberg GM, Bar-Ziv J, Danovitch G. Renal hamartomas and nephroblastomatosis with fetal gigantism: a familial syndrome. J Pediatr. 1973;83(3):414– 418. doi: 10.1016/s0022-3476(73)80264-1.
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36. Matsuura S, Matsumoto Y, Morishima K, et al. Monoallelic BUB1B mutations and defective mitoticspindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. Am J Med Genet A. 2006;140(4):358–367. doi: 10.1002/ajmg.a.31069.
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44. Rasmussen SA, Wong LY, Yang Q, et al. Populationbased analyses of mortality in trisomy 13 and trisomy 18. Pediatrics. 2003;111(4 Pt 1):777–784. doi: 10.1542/peds.111.4.777.
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Oncopediatrics. 2017; 4: 283-289
Wilm’s Tumor: Syndrome-Based and Molecular Diagnostics
https://doi.org/10.15690/onco.v4i4.1814Abstract
The genotype-phenotype correlations are quite often revealed in children with Wilm’s tumor. Phenotypedriven mutation detection provides the opportunity to predict a disease, to define and work out personal treatment course considering all the risks of possible complications. The article presents data on the main syndromes and genetically determined diseases associated with Wilm’s tumor. Patients with some WT1 associated syndromes (including WAGR and Denis–Drash), Perlman syndromes, the mosaic aneuploidy and Fanconi anemia due to biallelic BRCA2 mutation are at high risk of Wilm’s tumor development (>20%). Moderate risk of nephroblastoma development (5–20%) is registered in children with Fraser syndrome, Beckwith–Wiedemann syndrome with 11p15 disomy, and Sympson–Golabi–Behmel syndrome. Patients with the isolated hemihyipertrophy, Blооm syndrome, Li–Fraumeni syndrome, hyperparathyroid-jaw tumor (HPT-JT) syndromes, Mulibrey nanism, and other chromosomal aberrations seem to be at low risk for nephroblastoma (<5%). Future achievements in molecular biology will allow to develop new approaches to personalized treatment supplementing the treatment course with molecular target therapy in patients at high risk of disease recurrence.
References
1. Gleason JM, Lorenzo AJ, Bowlin PR, Koyle MA. Innovations in the management of Wilms’ tumor. Ther Adv Urol. 2014;6(4):165–176. doi: 10.1177/1756287214528023.
2. Wilms M. [Die Mischgeschwülste der Niere. In: Die Mischgeschwülste. (In German).] Leipzig: Verlag von Arthur Georgi; 1899.
3. Rivera MN, Haber DA. Wilms’ tumour: connecting tumorigenesis and organ development in the kidney. Nature Reviews Cancer. 2005;5(9):699–712. doi: 10.1038/nrc1696.
4. Breslow NE, Beckwith JB, Perlman EJ, Reeve AE. Age distributions, birth weights, nephrogenic rests, and heterogeneity in the pathogenesis of Wilms tumor. Pediatr Blood Cancer. 2006;47(3):260–267. doi: 10.1002/pbc.20891.
5. Stiller CA, Parkin DM. International variations in the incidence of childhood renal tumors. Br J Cancer. 1990;62(6):1026–1030. doi: 10.1038/bjc.1990.432.
6. Beckwith JB, Kiviat NB, Bonadio JF. Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms’ tumor. Pediatr Pathol. 1990;10(1–2):1–36. doi: 10.3109/15513819009067094.
7. Knudson AG. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971;68(4):820–823. doi: 10.1073/pnas.68.4.820.
8. Knudson AG, Jr., Strong LC. Mutation and cancer: a model for Wilms’ tumor of the kidney. J Natl Cancer Inst. 1972;48(2):313–324. doi: 10.1093/jnci/48.2.313.
9. Hoglund M, Gisselsson D, Hansen GB, Mitelman F. Wilms tumors develop through two distinct karyotypic pathways. Cancer Genet Cytogenet. 2004;150(1):9– 15. doi: 10.1016/j.cancerencyto.2003.08.017.
10. Scott RH, Stiller CA, Walker L, Rahman N. Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. J Med Genet. 2006;43(9):705– 715. doi: 10.1136/jmg.2006.041723.
11. Huff V. Genotype/phenotype correlations in Wilms’ tumor. Med Pediatr Oncol. 1996;27(5):408–414. doi: 10.1002/(SICI)1096-911X(199611)27:5<408::AIDMPO4>3.0.CO;2-Q.
12. Rose EA, Glaser T, Jones C, et al. Complete physical map of the WAGR region of 11p13 localizes a candidate Wilms’ tumor gene. Cell. 1990;60(3):495–508. doi: 10.1016/0092-8674(90)90600-J.
13. Royer-Pokora B, Beier M, Henzler M, et al. Twenty-four new cases of WT1 germline mutations and review of the literature: genotype/phenotype correlations for Wilms tumor development. Am J Med Genet A. 2004;127A(3):249–257. doi: 10.1002/ajmg.a.30015.
14. Ruteshouser EC, Robinson SM, Huff V. Wilms tumor genetics: Mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors. Genes Chromosomes & Cancer. 2008;47(6):461–470. doi: 10.1002/gcc.20553.
15. Scott RH, Douglas J, Baskcomb L, et al. Constitutional 11p15 abnormalities, including heritable imprinting center mutations, cause nonsyndromic Wilms tumor. Nat Genet. 2008;40(11):1329–1334. doi: 10.1038/ng.243.
16. Baird PN, Santos A, Groves N, et al. Constitutional mutations in the WT1 gene in patients with Denys- Drash syndrome. Hum Mol Genet. 1992;1(5):301– 305. doi: 10.1093/hmg/1.5.301.
17. Barbaux S, Niaudet P, Gubler MC, et al. Donor splicesite mutations in WT1 are responsible for Frasier syndrome. Nat Genet. 1997;17(4):467–470. doi: 10.1038/ng1297-467.
18. Demmer L, Primack W, Loik V, et al. Frasier syndrome: a cause of focal segmental glomerulosclerosis in a 46,XX female. J Am Soc Nephrol. 1999;10(10):2215– 2218.
19. McDonald JM, Douglass EC, Fisher R, et al. Linkage of familial Wilms’ tumor predisposition to chromosome 19 and a two-locus model for the etiology of familial tumors. Cancer Res. 1998;58(7):1387–1390.
20. Rahman N, Arbour L, Tonin P, et al. Evidence for a familial Wilms’ tumour gene (FWT1) on chromosome 17q12-q21. Nat Genet. 1996;13(4):461–463. doi: 10.1038/ng0896-461.
21. Rivera MN, Kim WJ, Wells J, et al. An X chromosome gene, WTX, is commonly inactivated in Wilms tumor. Science. 2007;315(5812):642–645. doi: 10.1126/science.1137509.
22. Wegert J, Wittmann S, Leuschner I, et al. WTX Inactivation Is a Frequent, but Late Event in Wilms Tumors Without Apparent Clinical Impact. Genes Chromosomes & Cancer. 2009;48(12):1102–1111. doi: 10.1002/gcc.20712.
23. DeBaun MR, Niemitz EL, McNeil DE, et al. Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects. Am J Hum Genet. 2002;70(3):604– 611. doi: 10.1086/338934.
24. Thavaraj V, Sethi A, Arya LS. Incomplete Beckwith-Wiedemann syndrome in a child with orbital rhabdomyosarcoma. Indian Pediatr. 2002;39(3):299–304.
25. Weksberg R, Nishikawa J, Caluseriu O, et al. Tumor development in the Beckwith- Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1. Hum Mol Genet. 2001;10(26):2989– 3000. doi: 10.1093/hmg/10.26.2989.
26. Weksberg R, Squire JA. Molecular biology of Beckwith-Wiedemann syndrome. Med Pediatr Oncol. 1996;27(5):462–469. doi: 10.1002/(SICI)1096-911X(199611)27:5<462::AID-MPO13>3.0.CO;2-C.
27. Bliek J, Gicquel C, Maas S, et al. Epigenotyping as a tool for the prediction of tumor risk and tumor type in patients with Beckwith-Wiedemann syndrome (BWS). J Pediatr. 2004;145(6):796–799. doi: 10.1016/j.jpeds.2004.08.007.
28. Rahman N. Mechanisms predisposing to childhood overgrowth and cancer. Curr Opin Genet Dev. 2005;15(3):227–233. doi: 10.1016/j.gde.2005.04.007.
29. Pilia G, HughesBenzie RM, MacKenzie A, et al. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet. 1996;12(3):241–247. doi: 10.1038/ng0396-241.
30. Mariani S, Iughetti L, Bertorelli R, et al. Genotype/phenotype correlations of males affected by Simpson- Golabi-Behmel syndrome with GPC3 gene mutations: Patient report and review of the literature. J Pediatr Endocrinol Metab. 2003;16(2):225–232. doi: 10.1515/jpem.2003.16.2.225.
31. Green DM, Breslow NE, Beckwith JB, Norkool P. Screening of children with hemihypertrophy, aniridia, and Beckwith-Wiedemann syndrome in patients with Wilms tumor: a report from the National Wilms Tumor Study. Med Pediatr Oncol. 1993;21(3):188– 192. doi: 10.1002/mpo.2950210307.
32. Niemitz EL, Feinberg AP, Brandenburg SA, et al. Children with idiopathic hemihypertrophy and Beckwith-Wiedemann syndrome have different constitutional epigenotypes associated with Wilms tumor. Am J Hum Genet. 2005;77(5):887–891. doi: 10.1086/497540.
33. Henneveld HT, van Lingen RA, Hamel BCJ, et al. Perlman syndrome: four additional cases and review. Am J Med Genet. 1999;86(5):439–446. doi: 10.1002/(sici)1096- 8628(19991029)86:5<439::aidajmg9>3.0.co;2-4.
34. Perlman M, Goldberg GM, Bar-Ziv J, Danovitch G. Renal hamartomas and nephroblastomatosis with fetal gigantism: a familial syndrome. J Pediatr. 1973;83(3):414– 418. doi: 10.1016/s0022-3476(73)80264-1.
35. Hanks S, Coleman K, Reid S, et al. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet. 2004;36(11):1159–1161. doi: 10.1038/ng1449.
36. Matsuura S, Matsumoto Y, Morishima K, et al. Monoallelic BUB1B mutations and defective mitoticspindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. Am J Med Genet A. 2006;140(4):358–367. doi: 10.1002/ajmg.a.31069.
37. Tischkowitz MD, Hodgson SV. Fanconi anaemia. J Med Genet. 2003;40(1):1–10. doi: 10.1136/jmg.40.1.1.
38. Ellis NA, Groden J, Ye TZ, et al. The Bloom’s syndrome gene product is homologous to RecQ helicases. Cell. 1995;83(4):655–666. doi:10.1016/0092-8674(95)90105-1.
39. Evans DG, Birch JM, Thorneycroft M, et al. Low rate of TP53 germline mutations in breast cancer/sarcoma families not fulfilling classical criteria for Li-Fraumeni syndrome. J Med Genet. 2002;39(12):941–944. doi: 10.1136/jmg.39.12.941.
40. Tan MH, Teh BT. Renal neoplasia in the hyperparathyroidism-jaw tumor syndrome. Curr Mol Med. 2004;4(8):895–897. doi: 10.2174/1566524043359719.
41. Kallijarvi J, Lahtinen U, Hamalainen R, et al. TRIM37 defective in mulibrey nanism is a novel RING finger ubiquitin E3 ligase. Exp Cell Res. 2005;308(1):146–155. doi: 10.1016/j.yexcr.2005.04.001.
42. Karlberg N, Jalanko H, Perheentupa J, Lipsanen-Nyman M. Mulibrey nanism: clinical features and diagnostic criteria. J Med Genet. 2004;41(2):92–98. doi: 10.1136/jmg.2003.014118.
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