BACKGROUND: Wilms tumor is the most common pediatric renal tumor and the fourth most common malignancy in children. Chromosome 16q deletion(del) or loss of heterozygosity (LOH) has been correlated with recurrence and overall poor prognosis, such that patients with 16qLOH and 1p allelic loss are treated with more aggressive chemotherapeutic regimens. METHODS: In the present study, we have compared the variant profiles of Wilms tumors with and without 16q del/LOH using both data available from the TARGET database (42 samples) and tumors procured from our legacy collection (8 samples). Exome-Seq data was analyzed for tumor specific variants mapping to 16q. Whole exome analysis was also performed. An unbiased approach for somatic variant analysis was used to detect tumor-specific, somatic variants. RESULTS: Of the 72 genes mapping to 16q, 42% were cilia-related genes and 28% of these were found to carry somatic variants specific to those tumors with 16qdel/LOH. Whole exome analyses further revealed that 30% of cilia-related genes across the genome carried alterations in tumors both with and without 16qdel/LOH. Additional pathway analyses revealed that many cilia-related pathway members also carried deleterious variant in these tumors including Sonic Hedgehog (SHh), Wnt, and Notch signaling pathways. CONCLUSIONS: The data suggest that cilia-related genes and pathways are compromised in Wilms tumors. The genes on chromosome 16q that carry deleterious variants in cilia-related genes may account for the more aggressive nature of tumors with 16q del/LOH. Copyright:
BACKGROUND:Wilms tumor is the most common pediatric renal tumor and the fourth most common malignancy in children. Chromosome 16q deletion(del) or loss of heterozygosity (LOH) has been correlated with recurrence and overall poor prognosis, such that patients with 16qLOH and 1p allelic loss are treated with more aggressive chemotherapeutic regimens. METHODS: In the present study, we have compared the variant profiles of Wilms tumors with and without 16q del/LOH using both data available from the TARGET database (42 samples) and tumors procured from our legacy collection (8 samples). Exome-Seq data was analyzed for tumor specific variants mapping to 16q. Whole exome analysis was also performed. An unbiased approach for somatic variant analysis was used to detect tumor-specific, somatic variants. RESULTS: Of the 72 genes mapping to 16q, 42% were cilia-related genes and 28% of these were found to carry somatic variants specific to those tumors with 16qdel/LOH. Whole exome analyses further revealed that 30% of cilia-related genes across the genome carried alterations in tumors both with and without 16qdel/LOH. Additional pathway analyses revealed that many cilia-related pathway members also carried deleterious variant in these tumors including Sonic Hedgehog (SHh), Wnt, and Notch signaling pathways. CONCLUSIONS: The data suggest that cilia-related genes and pathways are compromised in Wilms tumors. The genes on chromosome 16q that carry deleterious variants in cilia-related genes may account for the more aggressive nature of tumors with 16q del/LOH. Copyright:
Authors: Caroline Boerwinkle; Jan D Marshall; Joy Bryant; William A Gahl; Kenneth N Olivier; Meral Gunay-Aygun Journal: Pediatr Pulmonol Date: 2016-12-28
Authors: Wesley R Lewis; Erik B Malarkey; Douglas Tritschler; Raqual Bower; Raymond C Pasek; Jonathan D Porath; Susan E Birket; Sophie Saunier; Corinne Antignac; Michael R Knowles; Margaret W Leigh; Maimoona A Zariwala; Anil K Challa; Robert A Kesterson; Steven M Rowe; Iain A Drummond; John M Parant; Friedhelm Hildebrandt; Mary E Porter; Bradley K Yoder; Nicolas F Berbari Journal: PLoS Genet Date: 2016-07-29 Impact factor: 5.917
Authors: Samantha Gadd; Vicki Huff; Amy L Walz; Ariadne H A G Ooms; Amy E Armstrong; Daniela S Gerhard; Malcolm A Smith; Jaime M Guidry Auvil; Daoud Meerzaman; Qing-Rong Chen; Chih Hao Hsu; Chunhua Yan; Cu Nguyen; Ying Hu; Leandro C Hermida; Tanja Davidsen; Patee Gesuwan; Yussanne Ma; Zusheng Zong; Andrew J Mungall; Richard A Moore; Marco A Marra; Jeffrey S Dome; Charles G Mullighan; Jing Ma; David A Wheeler; Oliver A Hampton; Nicole Ross; Julie M Gastier-Foster; Stefan T Arold; Elizabeth J Perlman Journal: Nat Genet Date: 2017-08-21 Impact factor: 38.330