Abstract
As the pathogenesis of rhabdoid tumors (RT) relies on epigenetic disturbances a potential link to assisted reproductive technologies (ART) deserves further analyses.
METHODS
We analyzed patients conceived by ART (egg donation, ICSI, ivF) from EU-RHAB (n=8), the US (n=2), Iran (n=1), Lithuania (n=1) and Spain (n=1). Genetic and clinical evaluation included SMARCB1 and/or SMARCA4 (FISH, MLPA, sequencing) mutation analysis and immunohistochemistry.
RESULTS
Seven patients presented with AT/RT, four with extracranial RT and two demonstrated synchronous-, multifocal tumors. Metastases were present in 5 patients. Germline mutations (GLM) in SMARCB1 were detected in 4/9 (c.1110delG, c.141C>A, c.751delG, in one GLM not specified). Somatic mutations were analyzed in 8 children. The majority (69%) exhibited single nucleotide variants (c.1110delG, c.1148delC, c.197C>A, c.472C>T, c.141C>A, c.751delG), while partial/whole gene deletions (delTBX1_NIPSNAP1, delGNAZ_SMARCB1, delGNAZ_SEZ6L, delSMARCB1) were observed in 31%. A total resection (GTR) was achieved in 6/13. A total of 4 patients each received radiotherapy or HDCT. A CR was accomplished in 8 patients, three of them are alive 76, 72 and 10 months from diagnosis.
CONCLUSIONS
Children born following ART appear to be at risk for the development of RT. Our data warrant evaluation whether this risk is increased when compared to the occurrence of RT in the general population and what the epi-, genetic mechanisms for this phenomenon might be. Supported by grants to MCF by the “Deutsche Kinderkrebsstiftung” DKKS 2010.03 and the parents organization Lichtblicke, Augsburg.