This study presents a method for identifying somatically acquired genomic rearrangements in cancer using genome-wide massively parallel paired-end sequencing. The researchers analyzed two lung cancer cell lines, NCI-H2171 and NCI-H1770, to detect structural variations at the base-pair level. They identified 306 germline structural variants and 103 somatic rearrangements, revealing distinct patterns between germline and somatic changes. Somatic rearrangements were often found in amplified regions, including tandem duplications and fusion transcripts. Germline variants were primarily due to retrotransposition involving AluY and LINE elements. The study demonstrated the feasibility of systematically characterizing rearrangements in complex cancer genomes, offering new insights into cancer-associated genes. The researchers used paired-end sequencing to generate sequence reads from both ends of short DNA fragments, enabling the detection of rearrangements with high resolution. They identified 325 rearrangements in NCI-H2171 and 84 in NCI-H1770, including 244 germline and 62 somatic rearrangements. Many somatic rearrangements resulted in abnormal transcripts, such as fusion transcripts from interchromosomal rearrangements and internal tandem duplications. The study also identified tandem duplications, inverted duplications, and other structural variations, some of which were previously unknown. Copy number analysis revealed substantial amplifications in specific regions of the genome, with the most heavily amplified region in NCI-H2171 being on chromosome 8q24. The study developed a circular binary segmentation algorithm to analyze copy number changes, allowing for the identification of breakpoints and rearrangements. The results showed that the paired-end strategy could resolve somatic rearrangements that were previously undetectable by conventional karyotyping or FISH-based techniques. The study also identified fusion genes, such as the CACNA2D4-WDR43 fusion in NCI-H2171, which may contribute to oncogenesis. Additionally, the researchers found that some rearrangements occurred within or between amplicons, highlighting the complexity of cancer genomes. The study demonstrated the potential of massively parallel sequencing to identify previously unknown fusion genes and other rearrangements that may be relevant to cancer therapy. Overall, the findings underscore the importance of systematic, high-resolution analysis of genomic rearrangements in cancer research.This study presents a method for identifying somatically acquired genomic rearrangements in cancer using genome-wide massively parallel paired-end sequencing. The researchers analyzed two lung cancer cell lines, NCI-H2171 and NCI-H1770, to detect structural variations at the base-pair level. They identified 306 germline structural variants and 103 somatic rearrangements, revealing distinct patterns between germline and somatic changes. Somatic rearrangements were often found in amplified regions, including tandem duplications and fusion transcripts. Germline variants were primarily due to retrotransposition involving AluY and LINE elements. The study demonstrated the feasibility of systematically characterizing rearrangements in complex cancer genomes, offering new insights into cancer-associated genes. The researchers used paired-end sequencing to generate sequence reads from both ends of short DNA fragments, enabling the detection of rearrangements with high resolution. They identified 325 rearrangements in NCI-H2171 and 84 in NCI-H1770, including 244 germline and 62 somatic rearrangements. Many somatic rearrangements resulted in abnormal transcripts, such as fusion transcripts from interchromosomal rearrangements and internal tandem duplications. The study also identified tandem duplications, inverted duplications, and other structural variations, some of which were previously unknown. Copy number analysis revealed substantial amplifications in specific regions of the genome, with the most heavily amplified region in NCI-H2171 being on chromosome 8q24. The study developed a circular binary segmentation algorithm to analyze copy number changes, allowing for the identification of breakpoints and rearrangements. The results showed that the paired-end strategy could resolve somatic rearrangements that were previously undetectable by conventional karyotyping or FISH-based techniques. The study also identified fusion genes, such as the CACNA2D4-WDR43 fusion in NCI-H2171, which may contribute to oncogenesis. Additionally, the researchers found that some rearrangements occurred within or between amplicons, highlighting the complexity of cancer genomes. The study demonstrated the potential of massively parallel sequencing to identify previously unknown fusion genes and other rearrangements that may be relevant to cancer therapy. Overall, the findings underscore the importance of systematic, high-resolution analysis of genomic rearrangements in cancer research.