Additional file 7 of The Swedish childhood tumor biobank: systematic collection and molecular characterization of all pediatric CNS and other solid tumors in Sweden
Creators: name: Díaz de Ståhl, Teresita
name: Shamikh, Alia
name: Mayrhofer, Markus
name: Juhos, Szilvester
name: Basmaci, Elisa
name: Prochazka, Gabriela
name: Garcia, Maxime
name: Somarajan, Praveen Raj
name: Zielinska-Chomej, Katarzyna
name: Illies, Christopher
name: Øra, Ingrid
name: Siesjö, Peter
name: Sandström, Per-Erik
name: Stenman, Jakob
name: Sabel, Magnus
name: Gustavsson, Bengt
name: Kogner, Per
name: Pfeifer, Susan
name: Ljungman, Gustaf
name: Sandgren, Johanna
name: Nistér, Monica
Publisher: name: figshare
Year: 2024
Subjects: subject: Genetics
subject: FOS: Biological sciences

description: Additional file 7: Figure S3. Whole genome copy number profiles for selected samples with multiple structural variants. The tumor copy number status is indicated in different colors according to a scale (0 to 4) shown to the right in the figure. The copy number profile for the paired normal sample is shown in gray below the tumor track. A Highly rearranged genome profile in a tumor diagnosed as PNET (P2233_101T) and classified by methylation profiling as GBM IDH wild-type (though with lower score, 0.61). TP53 inactivation due to a somatic splice donor mutation plus LOH was observed. Numerous CNVs affecting almost all chromosomes and several focal amplifications were also detected, including amplification of EGFR on 7p11.2, KRAS on 12p12.1 (~70 DNA copies) and a nearby duplication (&gt; 50 DNA copies) creating a PLEKHA5::PIK3C2G fusion (Table 1, Additional file 2: Table S1). B A GBM (P2233_118T) that could not be assigned to a specific class by the methylation classifier showed many SVs, including numerous focal deletions within chrX, focal duplications and deletions on chr15, as well as a focal RB1 homozygous deletion (an extremely rare event in pediatric HGG). SV involving NTRK3 and a predicted fusion involving RERE::SLC2A5 were detected (Table 1, Additional file 2: Table S1). C An atypical meningioma (P2233_116T) displaying several copy number aberrations, including loss of chr22, which is a frequent event in pediatric meningiomas [32]. Multiple interchromosomal translocations were also observed on chr16, 19, 20 and 22, two of which involved NF2 (chr22:29638300 T]CHR12:131449186] and chr22:29645023 [CHR3:86137311[T) and led to NF2 transcript ablation. The tumor also displayed a focal amplification on 20q13.13, an event associated with progression and metastasis in several cancers. This locus encompasses, among others, ZFAS1, encoding a noncoding RNA that regulates the expression of genes involved in differentiation. An oncogenic role for ZFAS1 lncRNA has been described in head and neck squamous cell carcinomas [24]. D A relapsed rhabdoid meningioma (P2233_106T), for which the methylation classifier could not find a match. Rhabdoid meningioma is a rare, aggressive meningioma subtype. The sample presented with a highly rearranged genome with numerous SVs affecting almost all chromosomes, including deletion of chr22, encompassing NF2, an inversion on chr15 predicting a fusion between GABRA5 and NTRK3 and focal amplifications on chr5, several of them involving RICTOR. Focal homozygous deletions were also observed, one encompassing CDKN2A and another on 22q13.33, including SHANK3. Furthermore, the child carried a germline missense mutation in TP53 chr17:7674230 C/T rs28934575 245/393 G/S, with loss of the wild-type allele in the tumor (see Table 1, Additional file 2: Table S1.