Inferring absolute copy-number is more difficult because: (i) cancer cells are nearly always intermixed with an unknown fraction of normal cells (tumor purity); (ii) the actual DNA content of the cancer cells (ploidy), resulting from gross numerical and structural chromosomal abnormalities, is unknown 9, 10, 11, 12, 13 and (iii) the cancer cell population may be heterogeneous, perhaps due to ongoing subclonal evolution 14, 15. In principle, one could infer absolute copy-numbers by rescaling relative data based on cytological measurements of DNA mass per cancer cell16, 17, 18, or by single-cell sequencing approaches 15. However, such approaches are not suited to support initial large-scale efforts at comprehensive characterization of the cancer genome19.
