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We find hundreds of variants within known cancer-related genes detectable only through long-read sequencing. These findings highlight the need for long-read sequencing of cancer genomes for the precise analysis of their genetic instability.Many cancer genomes are extensively rearranged with aberrant chromosomal karyotypes. Deriving these karyotypes from high-throughput DNA sequencing of bulk tumor samples is complicated because most tumors are a heterogeneous mixture of normal cells and subpopulations of cancer cells, or clones, that h