%0 Generic
%A M.L., Thibodeau
%A M., Steinraths
%A L., Brown
%A Z., Zong
%A N., Shomer
%A S., Taubert
%A K.L., Mungall
%A Y.P., Ma
%A R., Mueller
%A I., Birol
%A A., Lehman
%D 2017
%T Supplementary Material for: Genomic and Cytogenetic Characterization of a Balanced Translocation Disrupting NUP98
%U https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Genomic_and_Cytogenetic_Characterization_of_a_Balanced_Translocation_Disrupting_NUP98/5363560
%R 10.6084/m9.figshare.5363560.v1
%2 https://karger.figshare.com/ndownloader/files/9217936
%2 https://karger.figshare.com/ndownloader/files/9217939
%2 https://karger.figshare.com/ndownloader/files/9217942
%2 https://karger.figshare.com/ndownloader/files/9217945
%2 https://karger.figshare.com/ndownloader/files/9217948
%2 https://karger.figshare.com/ndownloader/files/9217951
%2 https://karger.figshare.com/ndownloader/files/9217954
%2 https://karger.figshare.com/ndownloader/files/9217957
%K Balanced translocation
%K Pseudogene
%K Renal angiomyolipomas
%K Tuberous sclerosis
%K Whole-genome sequencing
%X A 41-year-old Asian woman with bilateral renal angiomyolipomas (AML) was incidentally identified to have a balanced translocation, 46,XX,t(11;12)(p15.4;q15). She had no other features or family history to suggest a diagnosis of tuberous sclerosis. Her healthy daughter had the same translocation and no renal AML at the age of 3 years. Whole-genome sequencing was performed on genomic maternal DNA isolated from blood. A targeted de novo assembly was then conducted with ABySS for chromosomes 11 and 12. Sanger sequencing was used to validate the translocation breakpoints. As a result, genomic characterization of chromosomes 11 and 12 revealed that the 11p breakpoint disrupted the NUP98 gene in intron 1, causing a separation of the promoter and transcription start site from the rest of the gene. The translocation breakpoint on chromosome 12q was located in a gene desert. NUP98 has not yet been associated with renal AML pathogenesis, but somatic NUP98 alterations are recurrently implicated in hematological malignancies, most often following a gene fusion event. We also found evidence for complex structural events involving chromosome 12, which appear to disrupt the TDG gene. We identified a TDGP1 partially processed pseudogene at 12p12.1, which adds complexity to the de novo assembly. In conclusion, this is the first report of a germline constitutional structural chromosome rearrangement disrupting NUP98 that occurred in a generally healthy woman with bilateral renal AML.
%I Karger Publishers