Bertil Johansson

Background: Individuals with Down syndrome have an elevated risk of childhood leukaemia and are suggested to have a reduced risk of solid tumours in adulthood. However, it remains unclear which cancer subtypes contribute to this pattern and the lifetime cancer risk. Methods: This Swedish population-based matched cohort study investigated age- and subtype-specific cancer risks in Down syndrome. National healthcare registers were used to include 9742 individuals with Down syndrome, born in Sweden between 1930–2017. Each individual was matched by birth year, sex, and birth county to 50 comparisons. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazard models. Results: Children with Down syndrome had a 20-fold increased risk of acute lymphoblastic leukaemia (ALL), and nearly a 500-fold increased risk of acute myeloid leukaemia (AML) before the age of 5. In contrast, individuals with Down syndrome had an overall lower risk of solid tumours, with significantly decreased risks for breast, prostate, lung, colorectal, gynaecological cancers, and melanoma, in adults. However, an increased risk was observed for testicular cancer and chondrosarcoma/chondroblastoma. Conclusion: We present the most comprehensive profile of cancer risk in Down syndrome, aiming to guide clinical practices, encourage tailored surveillance recommendations, and incite research on chromosome 21’s role in oncogenesis.

Table S2: Sequences of CRISPR gRNA to produce EPAS1 KO.

Table S6: Fish centromere counts.

Table S5: scWGS heterogeneity scores.

Cisplatin treatment of HCC1806 cells induced an altered transcriptome. A, Visualization of clusters of genetically similar cell populations (HCC1806) when untreated (red), and when resilient to treatment and large at 0 DPT (yellow), 5 DPT (green), and 10 DPT (blue). The PCA based on differentially expressed genes from the RNA-seq data. B, Visualization of gene expression of HCC1806 cells when untreated, surviving treatment at 0 DPT, 5 DPT, 10 DPT, and as progeny. Heat maps of the differentially expressed gene data. C, Visualization of downregulated and upregulated genes (fold change vs. adjusted P-value) in drug-resilient and transiently large HCC1806 cells at 10 DPT, compared with untreated control cells. D, Pathways upregulated in HCC1806 cells surviving at 10 DPT, as quantified with RNA-seq and Reactome analysis. E, Transcription factors regulating upregulated genes in HCC1806 cells surviving 10 DPT as quantified using RNA-seq and CHEA3 analysis.

Table S4: Well counts for single cell colonies two months after cisplatin treatment.

Figure S3: Cell diameter distributions for cell lines HCC1806, HCT116, and 786-0

Table S4: Well counts for single cell colonies two months after cisplatin treatment.

Methods S1: Filtration of treated cells