Exome Sequencing of an Adult Pituitary Atypical Teratoid Rhabdoid Tumor

Abstract

Atypical teratoid rhabdoid tumors (AT/RTs) are rare pediatric brain tumors characterized by bialleic loss of the SMARCB1 tumor suppressor gene. In contrast to pediatric AT/RT that has a simple genome, very little is known about the adult AT/RT genomic landscape. Using a combination of whole-exome sequencing and high-resolution SNP array in a single adult pituitary AT/RT, we identified a total of 47 non-synonymous mutations, of which 20 were predicted to cause non-conservative amino acid substitutions, in addition to a subclone of cells with trisomy 8. We suggest that adult AT/RT may not be markedly dissimilar to other adult brain tumors where mutations in a range of genes, reflecting the functional specialization of different brain regions, but including SMARCB1 inactivation, may be required for its pathogenesis.

Keywords: SMARCB1; adult; atypical teratoid rhabdoid tumor; copy number variation; exome sequencing; trisomy 8.

Figure 1

Summary of exome sequencing results comparing tumor and control skin tissue displayed as a Circos diagram. The outermost ring indicates chromosomes. The next ring summarizes DNA copy number and shows a scatter plot of the log2 ratio of normalized DNA concentration (RPKM) in the tumor and normal samples (red points). The green points indicate the inferred segmented copy number profile. The third ring from the outermost summarizes variant allele frequencies across the chromosomes (red points) and segmented allele frequencies (green points). The innermost ring indicates the positions of somatic SNP (circles) and indels (triangles). Somatic mutations likely to lead to a change in an encoded protein are colored green and those that are also included in the Cancer Gene Census list are colored red. All other somatic mutations are colored gray.