Infantile fibrosarcoma with TPM3-NTRK1 fusion in a boy with Bloom syndrome
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SHORT COMMUNICATION
Infantile fibrosarcoma with TPM3‑NTRK1 fusion in a boy with Bloom syndrome Sue M. Huson1 · Timo Staab2 · Marta Pereira1 · Heather Ward1 · Roberto Paredes3 · D. Gareth Evans1 · Daniel Baumhoer4 · James O’Sullivan1 · Ed Cheesman5 · Detlev Schindler2 · Stefan Meyer3,6,7 Received: 5 November 2019 / Accepted: 12 November 2020 © The Author(s) 2020
Abstract Bloom syndrome (BS) is a genomic and chromosomal instability disorder with prodigious cancer predisposition caused by pathogenic variants in BLM. We report the clinical and genetic details of a boy who first presented with infantile fibrosarcoma (IFS) at the age of 6 months and subsequently was diagnosed with BS at the age of 9 years. Molecular analysis identified the pathogenic germline BLM sequence variants (c.1642C>T and c.2207_2212delinsTAGATTC). This is the first report of IFS related to BS, for which we show that both BLM alleles are maintained in the tumor and demonstrate a TPM3-NTKR1 fusion transcript in the IFS. Our communication emphasizes the importance of long-term follow up after treatment for pediatric neoplastic conditions, as clues to important genetic entities might manifest later, and the identification of a heritable tumor predisposition often leads to changes in patient surveillance and management. Keywords Bloom syndrome · Infantile fibrosarcoma · Cancer predisposition · TPM3-NTKR1 fusion Abbreviations BS Bloom syndrome BLM Bloom syndrome helicase gene or protein IFS Infantile fibrosarcoma SCE Sister chromatid exchange
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10689-020-00221-1) contains supplementary material, which is available to authorized users. * Stefan Meyer [email protected] 1
Department of Genetic Medicine, St Mary’s Hospital, Central Manchester Foundation Trust, Manchester, UK
Department of Human Genetics, University of Würzburg, Würzburg, Germany
2
3
Stem Cell and Leukaemia Proteomics Laboratory, School of Cancer and Imaging Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
4
Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
Introduction Bloom syndrome (BS, OMIM #210900) is an autosomal recessively inherited genomic and chromosomal instability disorder with pre- and postnatal growth failure and skin photosensitivity, characteristically manifesting with a butterfly-like shaped facial rash [1]. Other skin changes include poikiloderma and pigmentation anomalies, which often appear later in life. Additional BS features comprise immunodeficiency, endocrine problems, chronic obstructive lung disease and exceptional predisposition to malignancies. BS is caused by pathogenic variants in the BLM gene, encoding a RecQ helicase [1]. The BLM 5
Department of Paediatric Histopathology, Royal Manchester Children’s Hospital, Central Manchester Foundation Trust, Manchester, UK
6
Departments of Paediatric Haematology Oncology, Royal Manches
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