Confined trisomy 8 mosaicism of meiotic origin: a rare cause of aneuploidy in childhood cancer.

Whether chromosome abnormalities observed in tumor cells may in some cases reflect low-grade somatic mosaicism for anomalies present already at zygote formation, rather than acquired somatic mutations, has for long remained a speculation. We here report a patient with Wilms tumor, where constitutional somatic mosaicism of trisomy 8 was detected in a previously healthy 2 ½-year-old boy. Single Nucleotide Polymorphism (SNP) array analysis of tumor tissue revealed a complex distribution of allele frequencies for chromosome 8 that could not be explained solely by mitotic events. Combined analysis of allele frequencies, chromosome banding, and fluorescence in situ hybridization revealed that the majority of tumor cells contained four copies of chromosome 8, with three distinct haplotypes at a 2:1:1 ratio. Because the patient had not been subject to organ transplantation, these findings indicated that the tumor karyotype evolved from a cell with trisomy 8 of meiotic origin, with subsequent somatic gain of one additional chromosome copy. Haplotype analysis was consistent with trisomy 8 through nondisjunction at meiosis I. Matched normal renal tissue or peripheral blood did not contain detectable amounts of cells with trisomy 8, consistent with the complete lack of mosaic trisomy 8 syndrome features in the patient. This case provides proof of principle for the hypothesis that tumor genotypes may in rare cases reflect meiotic rather than mitotic events, also in patients lacking syndromic features. © 2014 Wiley Periodicals, Inc.

Valind A ，Pal N ，Asmundsson J ，Gisselsson D ，Holmquist Mengelbier L ... -  《-》

Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis.

Conlin LK ，Thiel BD ，Bonnemann CG ，Medne L ，Ernst LM ，Zackai EH ，Deardorff MA ，Krantz ID ，Hakonarson H ，Spinner NB ... -  《-》

Partial trisomy 8 mosaicism not detected by cultured amniotic-fluid cells.

Prenatal detection of trisomy 8 mosaicism can be misleading and remains challenging in genetic counseling. Identifying cases of partial or complete trisomy 8 mosaicism will highlight the pitfalls of conventional karyotyping in prenatal amniocentesis for partial or complete trisomy 8 mosaicism. The patient was born uneventfully at term to a healthy 34-year-old mother. Analysis of the amniotic fluid (AF) cells showed a normal male karyotype. At birth, the newborn presented dysmorphic features, including asymmetric mandibles and ears, anteverted nostrils with a relatively long philtrum, retrognathia, and a clenched hand on the left side. Imaging studies revealed agenesis of the corpus callosum with bilateral colpocephaly, a common arterial trunk bifurcating into the left subclavian and carotid arteries, and bilateral pelviectasis. Cytogenetic analysis of the blood revealed mosaicism of partial trisomy 8: 47,XY,+del(8) (q21.3) [8]/46,XY [12]. Array comparative genomic hybridization (array-CGH) revealed 82.9 Mb duplications at chromosome 8p23.3-8q21.3 with dosage variations. Interphase fluorescence in situ hybridization analysis of urine sediments and buccal smears were compatible with mosaic compositions. A small colony of AF cells was found to have partial trisomy 8 in repeated analysis. Conventional karyotyping through amniocentesis has limitations particularly in detecting rare trisomy mosaicism if trisomic cells show growth disadvantage. Array-CGH using uncultured cells may be of help in providing more information on genetic dosage variations in such cases.

Tsai MC ，Cheng HY ，Su MT ，Chen M ，Kuo PL ... -  《-》

Constitutional partial 1q trisomy mosaicism and Wilms tumor.

Mark HF ，Wyandt H ，Pan A ，Milunsky JM ... -  《cancer genetics and cytogenetics》

Mosaic trisomy 17 in amniocytes: phenotypic outcome, tissue distribution, and uniparental disomy studies.

Genuardi M ，Tozzi C ，Pomponi MG ，Stagni ML ，Della Monica M ，Scarano G ，Calvieri F ，Torrisi L ，Neri G ... -  《EUROPEAN JOURNAL OF HUMAN GENETICS》