Genomic profile of two Brazilian choroid plexus tumors by whole-exome sequencing

Abstract

Choroid plexus tumors (CPTs) are rare intracranial neoplasms, representing <1% of all brain tumors, yet they represent 20% of first-year pediatric brain tumors. Although these tumors have been linked to TP53 germline mutations in the context of Li-Fraumeni syndrome, their somatic driver alterations remain poorly understood. In this study, we report two cases of lateral ventricle tumors: 3-yr-old male diagnosed with an atypical choroid plexus papilloma (aCPP), and a 6-mo-old female diagnosed with a choroid plexus carcinoma (CPC). We performed whole-exome sequencing of paired blood and tumor tissue in both patients, categorized somatic variants, and determined copy-number alterations. Our analysis revealed a tier II variant (Association for Molecular Pathology [AMP] criteria) in BRD1, a H3 and TP53 acetylation agent, in the aCPP. In addition, we detected copy-number gains on Chromosomes 12, 18, and 20 and copy-number losses on Chromosomes 13q and 22q (BRD1 locus) in this tumor. The CPC tumor had only a pathogenic germline TP53 variant, based on American College of Medical Genetics (ACMG) criteria, with a clinical and familiar history of Li-Fraumeni syndrome. The CPC patient presented loss of heterozygosity (LoH) of TP53 loci and hyperdiploid genome. Both tumors were microsatellite-stable. This is the first study performing whole-exome sequencing in Brazilian choroid plexus tumors, and in line with the literature, we corroborate the absence of recurrent somatic mutations in these tumors. Further studies with larger sample sizes are necessary to confirm our findings and better understand the underlying biology of these tumors.

Keywords: neoplasm of the nervous system.

Figure 1.

Choroid plexus atypical papilloma images. (A) Magnetic resonance imaging (MRI) revealing the tumor in the right ventricle. Hematoxylin and eosin–stained tissue sections. (B) Well-differentiated papillary pattern with a single-layered cell arrangement (10× magnification); (C) areas of solid growth and increased cellularity (40× magnification); (D) increased mitotic activity, arrows point to mitotic figures (40× magnification).

Figure 2.

Choroid plexus atypical papilloma molecular features. (A) Integrative genomics viewer (IGV) showing the BRD1 variant, showing the deletion only in the tumor tissue, represented as the black lines. (B) Choroid plexus atypical papilloma copy-number aberrations. The left blue lines indicate losses and the right red lines, the gains.

Figure 3.

Choroid plexus carcinoma images and hematoxylin and eosin–stained tissue sections. (A) Magnetic resonance imaging (MRI) of the choroid plexus carcinoma in the right ventricle. (B) Papillary fronds with irregular cell distribution. (C) Marked pleomorphism and increased mitotic activity.

Figure 4.

Family pedigree indicating the presence of Li–Fraumeni syndrome. Each affected family member's age at the time of diagnosis is listed below their symbol. The numbers inside each circles/squares/rhombus, indicates the number of offspring. The symbols with positive (+) sign indicate the presence of germline TP53 variant, which was detected by Sanger sequencing. Conversely, symbols with negative (−) sign indicate the absence of variant. (Circles) female, (squares) males, and (rhombus) unknown sex. The arrow shows the proband who was the subject of the whole-exome sequencing.

Figure 5.

Choroid plexus papilloma molecular features. (A) Integrative genomics viewer (IGV) showing the TP53 variant (T to C substitution), in both blood (germline) and tumor tissue. (B) Copy-number aberrations. The left blue lines indicate losses and the right red lines, the gains.