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Familial Cancer
Published in: Familial Cancer 4/2012

01-12-2012 | Short Communication

Heterozygote FANCD2 mutations associated with childhood T Cell ALL and testicular seminoma

Authors: Stephanie Smetsers, Joanne Muter, Claire Bristow, Leena Patel, Kate Chandler, Denise Bonney, Robert F. Wynn, Anthony D. Whetton, Andrew M. Will, Davy Rockx, Hans Joenje, Gordon Strathdee, Jonathan Shanks, Eva Klopocki, Johan J. P. Gille, Josephine Dorsman, Stefan Meyer

Published in: Familial Cancer | Issue 4/2012

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Abstract

Fanconi anaemia (FA) is an inherited disease with congenital and developmental abnormalities characterised by cellular cross linker hypersensitivity. FA is caused by mutations in any of so far 15 identified FANC genes, which encode proteins that interact in a common DNA damage response (DDR) pathway. Individuals with FA have a high risk of developing acute myeloid leukaemia (AML) and squamous cell carcinoma. An increased cancer risk has been firmly established for carriers of mutations in FANCD1/BRCA2, FANCJ/BRIP1, FANCN/PALB2, RAD51C/FANCO and link the FA pathway to inherited breast and ovarian cancer. We describe a pedigree with FANCD2 mutations c.458T > C (p.Leu153Ser) and c.2715 + 1G > A (p.Glu906LeufsX4) with mild phenotype FA in the index case, T cell ALL in the Leu153Ser heterozygous brother and testicular seminoma in the p.Glu906LeufsX4 heterozygous father. Both FANCD2 alleles were present in the T Cell ALL and the seminoma. This links specific FANCD2 mutations to T cell ALL and seminoma without evidence of allelic loss in the tumour tissue.
Literature
1.
de Winter JP, Joenje H (2009) The genetic and molecular basis of Fanconi anemia. Mutat Res 668(1–2):11–19PubMed
2.
Kim Y, Lach FP, Desetty R, Hanenberg H, Auerbach AD, Smogorzewska A (2010) Mutations of the SLX4 gene in Fanconi anemia. Nat Genet 43(2):142–146CrossRef
3.
Stoepker C, Hain K, Schuster B et al (2010) SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype. Nat Genet 43(2):138–141CrossRef
4.
Vaz F, Hanenberg H, Schuster B et al (2010) Mutation of the RAD51C gene in a Fanconi anemia-like disorder. Nat Genet 42(5):406–409PubMedCrossRef
5.
Rosenberg PS, Alter BP, Ebell W (2008) Cancer risks in Fanconi anemia: findings from the German Fanconi Anemia Registry. Haematologica 93(4):511–517PubMedCrossRef
6.
Rosenberg PS, Greene MH, Alter BP (2003) Cancer incidence in persons with Fanconi anemia. Blood 101(3):822–826PubMedCrossRef
7.
Tischkowitz M, Dokal I (2004) Fanconi anaemia and leukaemia—clinical and molecular aspects. Br J Haematol 126(2):176–191PubMedCrossRef
8.
Wooster R, Neuhausen SL, Mangion J et al (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science (New York, NY 265(5181): 2088–2090
9.
Rahman N, Seal S, Thompson D et al (2007) PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 39(2):165–167PubMedCrossRef
10.
Meindl A, Hellebrand H, Wiek C et al (2010) Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat Genet 42(5):410–414PubMedCrossRef
11.
12.
13.
Ameziane N, Errami A, Leveille F et al (2008) Genetic subtyping of Fanconi anemia by comprehensive mutation screening. Hum Mutat 29(1):159–166PubMedCrossRef
14.
Borriello A, Locasciulli A, Bianco AM et al (2007) A novel Leu153Ser mutation of the Fanconi anemia FANCD2 gene is associated with severe chemotherapy toxicity in a pediatric T-cell acute lymphoblastic leukemia. Leukemia 21(1):72–78PubMedCrossRef
15.
Kalb R, Neveling K, Hoehn H et al (2007) Hypomorphic mutations in the gene encoding a key Fanconi anemia protein, FANCD2, sustain a significant group of FA-D2 patients with severe phenotype. Am J Hum Genet 80(5):895–910PubMedCrossRef
16.
LeBron C, Pal P, Brait M et al (2011) Genome-wide analysis of genetic alterations in testicular primary seminoma using high resolution single nucleotide polymorphism arrays. Genomics 97(6):341–349PubMedCrossRef
17.
Alter BP, Rosenberg PS, Brody LC (2007) Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2. J Med Genet 44(1):1–9PubMedCrossRef
18.
Rischewski JR, Clausen H, Leber V et al (2000) A heterozygous frameshift mutation in the Fanconi anemia C gene in familial T-ALL and secondary malignancy. Klin Padiatr 212(4):174–176PubMedCrossRef
19.
Holzel M, van Diest PJ, Bier P et al (2003) FANCD2 protein is expressed in proliferating cells of human tissues that are cancer-prone in Fanconi anaemia. J Pathol 201(2):198–203PubMedCrossRef
20.
Lin YJ, Lan YC, Wan L et al (2010) The NBS1 genetic polymorphisms and the risk of the systemic lupus erythematosus in Taiwanese patients. J Clin Immunol 30(5):643–648PubMedCrossRef
21.
Davies RC, Pettijohn K, Fike F et al (2011) DNA double strand break repair is defective in pediatric systemic lupus erythematosus. Arthr Rheum
Metadata
Title
Heterozygote FANCD2 mutations associated with childhood T Cell ALL and testicular seminoma
Authors
Stephanie Smetsers
Joanne Muter
Claire Bristow
Leena Patel
Kate Chandler
Denise Bonney
Robert F. Wynn
Anthony D. Whetton
Andrew M. Will
Davy Rockx
Hans Joenje
Gordon Strathdee
Jonathan Shanks
Eva Klopocki
Johan J. P. Gille
Josephine Dorsman
Stefan Meyer
Publication date
01-12-2012
Publisher
Springer Netherlands
Published in
Familial Cancer / Issue 4/2012
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI
https://doi.org/10.1007/s10689-012-9553-3

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