Decreased CDKN1C Expression in Congenital Alveolar Rhabdomyosarcoma Associated with Beckwith-Wiedemann Syndrome

Overview

Journal Indian J Pediatr

Specialty Pediatrics

Date 2016 Jun 28

PMID 27345568

Citations 4

Authors

Fiammetta Piersigilli

Cinzia Auriti

Vito Mondi

Paola Francalanci

Guglielmo Salvatori

Olivier Danhaive

Affiliations

Soon will be listed here.

Abstract

The Beckwith-Wiedemann syndrome (BWS) is a genetic disorder characterized by somatic overgrowth and predisposition to embryonal tumors, such as Wilm's tumor, hepatoblastoma, neuroblastoma and rhabdomyosarcoma (RMS). BWS is associated with various genetic alterations: a variety of molecular lesions are described on the chromosome 11p15, affecting gene expression for IGF2, H19, CDKN1C and KCNQ1OT1. Alveolar RMS also recognises characteristic genetic alterations: two types of translocations, t(2,13) or t(1,13), that generate the PAX3-FKHR or PAX7-FKHR fusion proteins. It has been postulated however, that in BWS this kind of tumor occurs without this characteristic chromosomal rearrangement. The authors describe case of a neonate with BWS that presented at birth with cutaneous metastasis due to alveolar RMS. Genetic analysis showed lack of the two characteristic translocations in the tumor tissue, supporting a different oncogenic pathway of alveolar RMS in children with BWS.

Citing Articles

Clinical Spectrum and Tumour Risk Analysis in Patients with Beckwith-Wiedemann Syndrome Due to Pathogenic Variants.

Cardoso L, Parra A, Gil C, Arias P, Gallego N, Romanelli V Cancers (Basel). 2022; 14(15).

PMID: 35954470 PMC: 9367242. DOI: 10.3390/cancers14153807.

Malignant Superficial Mesenchymal Tumors in Children.

Drabent P, Fraitag S Cancers (Basel). 2022; 14(9).

PMID: 35565289 PMC: 9104419. DOI: 10.3390/cancers14092160.

Retracted Article: Long non-coding RNA KCNQ1OT1 promotes osteosarcoma progression by increasing β-catenin activity.

Zhang C, Du S, Cao L RSC Adv. 2022; 8(66):37581-37589.

PMID: 35558611 PMC: 9089326. DOI: 10.1039/c8ra07209d.

Germline predisposition to genitourinary rhabdomyosarcoma.

Schneider K, Cost N, Schultz K, Svihovec S, Suttman A Transl Androl Urol. 2020; 9(5):2430-2440.

PMID: 33209717 PMC: 7658107. DOI: 10.21037/tau-20-76.

References

Mondi V, Piersigilli F, Salvatori G, Auriti C . The Skin as an Early Expression of Malignancies in the Neonatal Age: A Review of the Literature and a Case Series. Biomed Res Int. 2016; 2015:809406. PMC: 4698537. DOI: 10.1155/2015/809406. View

Ferrari A, Orbach D, Sultan I, Casanova M, Bisogno G . Neonatal soft tissue sarcomas. Semin Fetal Neonatal Med. 2012; 17(4):231-238. DOI: 10.1016/j.siny.2012.05.003. View

Pettenati M, Haines J, Higgins R, Wappner R, Palmer C, Weaver D . Wiedemann-Beckwith syndrome: presentation of clinical and cytogenetic data on 22 new cases and review of the literature. Hum Genet. 1986; 74(2):143-54. DOI: 10.1007/BF00282078. View

Diaz-Meyer N, Day C, Khatod K, Maher E, Cooper W, Reik W . Silencing of CDKN1C (p57KIP2) is associated with hypomethylation at KvDMR1 in Beckwith-Wiedemann syndrome. J Med Genet. 2003; 40(11):797-801. PMC: 1735305. DOI: 10.1136/jmg.40.11.797. View

Weksberg R, Nishikawa J, Caluseriu O, Fei Y, Shuman C, Wei C . 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. View

DeBaun M, Tucker M . Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry. J Pediatr. 1998; 132(3 Pt 1):398-400. DOI: 10.1016/s0022-3476(98)70008-3. View

Dillon P, Whalen T, Azizkhan R, Haase G, Coran A, King D . Neonatal soft tissue sarcomas: the influence of pathology on treatment and survival. Children's Cancer Group Surgical Committee. J Pediatr Surg. 1995; 30(7):1038-41. DOI: 10.1016/0022-3468(95)90337-2. View

Habib W, Azzi S, Brioude F, Steunou V, Thibaud N, Das Neves C . Extensive investigation of the IGF2/H19 imprinting control region reveals novel OCT4/SOX2 binding site defects associated with specific methylation patterns in Beckwith-Wiedemann syndrome. Hum Mol Genet. 2014; 23(21):5763-73. DOI: 10.1093/hmg/ddu290. View

Smith A, Squire J, Thorner P, Zielenska M, Shuman C, Grant R . Association of alveolar rhabdomyosarcoma with the Beckwith-Wiedemann syndrome. Pediatr Dev Pathol. 2002; 4(6):550-8. DOI: 10.1007/s10024001-0110-6. View

10.

Rodriguez-Galindo C, Hill D, Onyekwere O, Pin N, Rao B, Hoffer F . Neonatal alveolar rhabdomyosarcoma with skin and brain metastases. Cancer. 2001; 92(6):1613-20. DOI: 10.1002/1097-0142(20010915)92:6<1613::aid-cncr1487>3.0.co;2-n. View

11.

Lobe T, Wiener E, Hays D, LAWRENCE W, Andrassy R, Johnston J . Neonatal rhabdomyosarcoma: the IRS experience. J Pediatr Surg. 1994; 29(8):1167-70. DOI: 10.1016/0022-3468(94)90302-6. View

12.

Hayashi K, Ohtsuki Y, Takahashi K, Sonobe H, Nakamura S, Kitagawa N . Congenital alveolar rhabdomyosarcoma with multiple skin metastases. Report of a case. Acta Pathol Jpn. 1988; 38(2):241-8. DOI: 10.1111/j.1440-1827.1988.tb01102.x. View

13.

Pappas J . The clinical course of an overgrowth syndrome, from diagnosis in infancy through adulthood: the case of Beckwith-Wiedemann syndrome. Curr Probl Pediatr Adolesc Health Care. 2015; 45(4):112-7. DOI: 10.1016/j.cppeds.2015.03.001. View

14.

Romanelli V, Belinchon A, Benito-Sanz S, Martinez-Glez V, Gracia-Bouthelier R, Heath K . CDKN1C (p57(Kip2)) analysis in Beckwith-Wiedemann syndrome (BWS) patients: Genotype-phenotype correlations, novel mutations, and polymorphisms. Am J Med Genet A. 2010; 152A(6):1390-7. DOI: 10.1002/ajmg.a.33453. View

15.

Weksberg R, Shen D, Fei Y, Song Q, Squire J . Disruption of insulin-like growth factor 2 imprinting in Beckwith-Wiedemann syndrome. Nat Genet. 1993; 5(2):143-50. DOI: 10.1038/ng1093-143. View

16.

Pateras I, Apostolopoulou K, Niforou K, Kotsinas A, Gorgoulis V . p57KIP2: "Kip"ing the cell under control. Mol Cancer Res. 2009; 7(12):1902-19. DOI: 10.1158/1541-7786.MCR-09-0317. View

17.

Kuroiwa M, Sakamoto J, Shimada A, Suzuki N, Hirato J, Park M . Manifestation of alveolar rhabdomyosarcoma as primary cutaneous lesions in a neonate with Beckwith-Wiedemann syndrome. J Pediatr Surg. 2009; 44(3):e31-5. DOI: 10.1016/j.jpedsurg.2008.12.010. View