TABLE 1.
Study | Frequency of Mutations | Sample Size | Sequencing Technique | Evaluation of Tumor Cellularity |
---|---|---|---|---|
Alexandrov et al50 | The median number of mutations per Mega base is 1, ranging from 0.1 to 10 mutations per Mega base (ie, 280 to 28,000 mutations per patient) | ~120 | Either whole genome sequencing (15 samples) and whole exome sequencing (the remaining samples). | |
Jones et al51 | The average number of mutations detected per patient is 48 | 24 | Microarrays-based exome sequencing: protein-coding exons from more than 20,000 genes were identified. Then, using microarrays containing probes for ~106 single-nucleotide polymorphisms, homozygous deletions and amplifications in the tumor samples were detected. | To remove contaminating non-neoplastic cells, tumor samples were passaged in vitro as cell lines or in nude mice. Then, to validate somatic mutations, exons containing variant sequences were reamplified and resequenced from both tumor and normal tissues |
Biankin et al19 | The average number of mutations detected per patient is 26, ranging from 1 to 116. | 99 | Whole exome sequencing: using exome capturing and sequencing of different mixtures of cancer cell line and matched germline DNA as a standard, tumor samples with greater than 20% epithelial cellularity and/or ≥10 validated somatic mutations were included in the study. The average sequence depth was 26,608-fold, ranging from 609 to 213,544. | The cellularity of each primary sample was estimated through pathological review, deep amplicon-based sequencing of exons 2 and 3 of KRAS and single nucleotide polymorphism (SNP) array-based cellularity estimates. |
Balachandran et al, the MSKCC cohort52 | The median number of mutations detected per patient is 171 The median number of neoantigen-related mutations detected per patient is 38 |
58 | Whole exome sequencing: whole exome sequencing was performed at 150× coverage for tumor samples and 70× for matched normal | Only tumor islands of more than 70% cellularity were included in the study based on expert PDAC pathologic review. |
Balachandran et al, the ICGC cohort52 | The median number of mutations detected per is 135 The median number of neoantigen-related mutations detected per patient is 32 |
166 | Either whole genome sequencing or whole exome sequencing: primary tumors and patient-derived cell lines with more than 40% cellularity underwent whole genome sequencing at 75× mean coverage. Samples with 12–40% cellularity underwent deep-exome sequencing at 400× mean coverage. | Tumor cellularity was estimated for each sample using a combination of qPure analysis and KRAS amplicon sequencing. |
Waddell et al54 | The average number of mutations per Mega base is 2.64, ranging from 0.65 to 28.2 mutations per Mega base (ie, 1820 to 78,960 mutations per patient) | 100 | Whole-genome sequencing: Tumor samples with more than 40% cellularity and patient-derived cell lines whole genome sequencing at 65× mean coverage and compared to the germline at an average coverage of 38× |
Tumor cellularity was estimated for each sample using qPure analysis |
Bailey et al41 | The median number of coding mutations detected per patient is 62 The number of neoantigen-related mutations detected per sample ranges from 4 to 4000 |
456 | Either whole genome sequencing or whole exome sequencing: primary tumors and patient-derived cell lines with more than 40% cellularity underwent whole genome sequencing at 75× mean coverage. Samples with 12–40% cellularity underwent deep-exome sequencing at 400× mean coverage. | Tumor cellularity was estimated for each sample using a combination of qPure analysis and KRAS amplicon sequencing. |
Bailey et al65 |