Top

Published in:

Open Access 01-12-2010 | Case report

Monozygotic twins with Neurofibromatosis type 1, concordant phenotype and synchronous development of MPNST and metastasis

Authors: German Melean, Alba Marina Hernández, María Carmen Valero, Elisabete Hernández-Imaz, Yolanda Martín, Concepción Hernández-Chico

Published in: BMC Cancer | Issue 1/2010

Abstract

Background

Neurofibromatosis type 1 is a common autosomal dominant disorder with full penetrance and variable expression. The condition predisposes individuals to the development of malignant nervous system tumours, most frequently Malignant Peripheral Nerve Sheath Tumours (MPNSTs). Previous studies indicate that genetic factors other than mutations in NF1 may be responsible for the condition's variable expression.

Case report

Here we present data from a pair of monozygotic twins affected by Neurofibromatosis type 1 resulting from a de novo mutation. Both twins developed a left sciatic plexiform neurofibroma that evolved into MPNST at a similar age and they also developed pulmonary metastasis at the same age. Other concordant traits between the twins were: macrocephaly, psychomotor delay, café-au-lait spots, cutaneous neurofibromas, retroperitoneal, pleural and paraspinal neurofibromas. The main discordant features observed were tibial pseudoarthrosis, pectus carinatum, osteoporosis and thymus hyperplasia.

Conclusions

This is the first report of monozygotic twins with Neurofibromatosis type 1 that develop MPNSTs, the localization and chronological evolution of which, and its metastasis, is concordant in both twins. These cases suggest that the events involved in the transformation of benign plexiform neurofibromas to MPNSTs in Neurofibromatosis type 1, follow a spatiotemporally programme that is influenced by heritable factors other than NF1 mutations.

Ballester R, Marchuk D, Boguski M, Saulino A, Letcher R, Wigler M, Collins F: The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell. 1990, 63: 851-859. 10.1016/0092-8674(90)90151-4.CrossRefPubMed

Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL: Neurofibromatosis type 1 revisited. Pediatrics. 2009, 123: 124-133. 10.1542/peds.2007-3204.CrossRefPubMed

Upadhyaya M, Spurlock G, Monem B, Thomas N, Friedrich RE, Kluwe L, Mautner V: Germline and somatic NF1 gene mutations in plexiform neurofibromas. Hum Mutat. 2008, 29: E103-E111. 10.1002/humu.20793.CrossRefPubMed

Ferner RE, Gutmann DH: International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis. Cancer Res. 2002, 62: 1573-1577.PubMed

Thomson SA, Fishbein L, Wallace MR: NF1 mutations and molecular testing. J Child Neuro. 2002, 17: 555-561. 10.1177/088307380201700803.CrossRef

Valero MC, Pascual-Castroviejo I, Velasco E, Moreno F, Hernández-Chico C: Identification of de novo deletions at the NF1 gene: no preferential paternal origin and phenotypic analysis of patients. Hum Genet. 1997, 99: 720-726. 10.1007/s004390050438.CrossRefPubMed

Pasmant E, Sabbagh A, Spurlock G, Laurendeau I, Grillo E, Hamel MJ, Martin L, Barbarot S, Leheup B, Rodriguez D, Lacombe D, Dollfus H, Pasquier L, Isidor B, Ferkal S, Soulier J, Sanson M, Dieux-Coeslier A, Bièche I, Parfait B, Vidaud M, Wolkenstein P, Upadhyaya M, Vidaud D, members of the NF France Network: NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype. Hum Mutat. 2010, 31: E1506-E1518. 10.1002/humu.21271.CrossRefPubMed

Upadhyaya M, Huson SM, Davies M, Thomas N, Chuzhanova N, Giovannini S, Evans DG, Howard E, Kerr B, Griffiths S, Consoli C, Side L, Adams D, Pierpont M, Hachen R, Barnicoat A, Li H, Wallace P, Van Biervliet JP, Stevenson D, Viskochil D, Baralle D, Haan E, Riccardi V, Turnpenny P, Lazaro C, Messiaen L: An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene (c.2970-2972 delAAT): evidence of a clinically significant NF1 genotype-phenotype correlation. Am J Hum Genet. 2007, 80: 140-151. 10.1086/510781.CrossRefPubMed

Easton DF, Ponder MA, Huson SM, Ponder BA: An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes. Am J Hum Genet. 1993, 53: 305-301.PubMedPubMedCentral

10.

Sabbagh A, Pasmant E, Laurendeau I, Parfait B, Barbarot S, Guillot B, Combemale P, Ferkal S, Vidaud M, Aubourg P, Vidaud D, Wolkenstein P, members of the NF France Network: Unravelling the genetic basis of variable clinical expression in neurofibromatosis 1. Hum Mol Genet. 2009, 18: 2768-2778. 10.1093/hmg/ddp212.CrossRefPubMedPubMedCentral

11.

Szudek J, Joe H, Friedman JM: Analysis of intrafamilial phenotypic variation in neurofibromatosis 1 (NF1). Genet Epidemiol. 2002, 23: 150-164. 10.1002/gepi.1129.CrossRefPubMed

12.

Szudek J, Evans DG, Friedman JM: Patterns of associations of clinical features in neurofibromatosis 1 (NF1). Hum Genet. 2003, 112: 289-297.PubMed

13.

Fahsold R, Hoffmeyer S, Mischung C, Gille C, Ehlers C, Kücükceylan N, Abdel-Nour M, Gewies A, Peters H, Kaufmann D, Buske A, Tinschert S, Nürnberg P: Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain. Am J Hum Genet. 2000, 66: 790-818. 10.1086/302809.CrossRefPubMedPubMedCentral

14.

Bahadir C, Gürleyik G, Ocak E: Neurofibromatosis type 1 and primary hyperparathyroidism with spinal deformity and osteoporosis. Acta Chir Belg. 2009, 109: 123-125.CrossRefPubMed

15.

Carroll SL, Ratner N: How does the Schwann cell lineage form tumors in NF1?. Glia. 2008, 56: 1590-1605. 10.1002/glia.20776.CrossRefPubMedPubMedCentral

16.

Thomas L, Kluwe L, Chuzhanova N, Mautner V, Upadhyaya M: Analysis of NF1 somatic mutations in cutaneous neurofibromas from patients with high tumor burden. Neurogenetics.

17.

Spurlock G, Knight SJ, Thomas N, Kiehl TR, Guha A, Upadhyaya M: Molecular evolution of a neurofibroma to malignant peripheral nerve sheath tumor (MPNST) in an NF1 patient: correlation between histopathological, clinical and molecular findings. J Cancer Res Clin Oncol.

18.

Miller SJ, Jessen WJ, Mehta T, Hardiman A, Sites E, Kaiser S, Jegga AG, Li H, Upadhyaya M, Giovannini M, Muir D, Wallace MR, Lopez E, Serra E, Nielsen GP, Lazaro C, Stemmer-Rachamimov A, Page G, Aronow BJ, Ratner N: Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene. EMBO Mol Med. 2009, 1: 236-248. 10.1002/emmm.200900027.CrossRefPubMedPubMedCentral

19.

Ottini L, Esposito DL, Richetta A, Carlesimo M, Palmirotta R, Verí MC, Battista P, Frati L, Caramia FG, Calvieri S, Cama A, Mariani-Costantini R: Alterations of microsatellites in neurofibromas of von Recklinghausen's disease. Cancer Res. 1995, 55: 5677-5680.PubMed

20.

Scott RH, Mansour S, Pritchard-Jones K, Kumar D, MacSweeney F, Rahman N: Medulloblastoma, acute myelocytic leukemia and colonic carcinomas in a child with biallelic MSH6 mutations. Nat Clin Pract Oncol. 2007, 4: 130-134. 10.1038/ncponc0719.CrossRefPubMed

21.

Bandipalliam P: Syndrome of early onset colon cancers, hematologic malignancies & features of neurofibromatosis in HNPCC families with homozygous mismatch repair gene mutations. Fam Cancer. 2005, 4: 323-333. 10.1007/s10689-005-8351-6.CrossRefPubMed

22.

Lubinsky MS: Non-random associations and vascular fields in neurofibromatosis 1: a pathogenetic hypothesis. Am J Med Genet A. 2006, 140: 2080-2084.CrossRefPubMed

23.

Wistuba II, Tomlinson GE, Behrens C, Virmani A, Geradts J, Blum JL, Minna JD, Gazdar AF: Two identical triplet sisters carrying a germline BRCA1 gene mutation acquire very similar breast cancer somatic mutations at multiple other sites throughout the genome. Genes Chromosomes Cancer. 2000, 28: 359-369. 10.1002/1098-2264(200008)28:4<359::AID-GCC1>3.0.CO;2-N.CrossRefPubMed

24.

Delgado L, Fernández G, González A, Bressac-de Paillerets B, Gualco G, Bombled J, Cataldi S, Sabini G, Roca R, Musé IM: Hereditary breast cancer associated with a germline BRCA2 mutation in identical female twins with similar disease expression. Cancer Genet Cytogenet. 2002, 133: 24-28. 10.1016/S0165-4608(01)00541-6.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/10/407/prepub

Title: Monozygotic twins with Neurofibromatosis type 1, concordant phenotype and synchronous development of MPNST and metastasis
Authors: German Melean
Alba Marina Hernández
María Carmen Valero
Elisabete Hernández-Imaz
Yolanda Martín
Concepción Hernández-Chico
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-10-407

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Case report

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2010

Cancer resistance of SR/CR mice in the genetic knockout backgrounds of leukocyte effector mechanisms: determinations for functional requirements

Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B Overexpression in HCC

Phenotypic effects of the circadian gene Cryptochrome 2 on cancer-related pathways

Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways

A long-term follow-up of the imatinib mesylate treatment for the patients with recurrent gastrointestinal stromal tumor (GIST): the liver metastasis and the outcome

Identification of S100A8-correlated genes for prediction of disease progression in non-muscle invasive bladder cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer