Data for: Principles of subclonal gene dosage across human cancers

The group of samples come from cancer patients diagnosed in Swedish hospitals. The cancer patients had been diagnosed with pediatric acute lymphoblastic leukemia (n:15), acute myeloid leukemia (n:5), melanoma (n:2), sarcomas (n:11) or breast cancer (n:11).

Samples from cancer patients were collected through bone marrow sampling (leukemias) or after surgical resection (solid tumours). Bone marrow samples were depleted of red blood cells and stored in FBS+10%DMSO until further processing. Surgically resected tumors were enzymatically and mechanically dissociated before being stored in FBS+10%DMSO. Samples were then processed by performing dead cell removal, and antibody staining to enrich for tumor cells by flow cytometry. Single cells (~500 per patient) were sorted into 384 well plates and the plates were processed using DNTR-seq, see "A Highly Scalable Method for Joint Whole-Genome Sequencing and Gene-Expression Profiling of Single Cells" at doi:10.1016/j.molcel.2020.09.025, which enables WGS and mRNA sequencing on individual cells. Data was analyzed using ASCENT (Absolute Single cell Copy number Evaluation and subcloNe Topology), described thoroughly in "Absolute copy number aware CNV calling of sub-megabase segments in ultra-low coverage single-cell DNA sequencing data", see doi:https://doi.org/10.1093/nar/gkaf919, enabling the study of genetic clones, identified by CNVs (Copy number variations) and their expression patterns.

We selected different cancer types, known to have different levels and types of CNVs for this study. This included pediatric acute lymphoblastic leukemia (known to have few but large CNVs) acute myeloid leukemia (large CNVs), melanoma (mainly characterized by Single nucleotide variants, SNVs) or breast cancer (multiple small and large CNVs). The leukemia samples originated from bone marrow aspirations taken at diagnosis of the disease. Breast cancer and sarcoma samples originate from surgical resection (without neoadjuvant treatment), following diagnosis. The melanoma samples were metastatic and originated from surgical resections.