Dr. Collisson has disclosed that he receives support from the Doris Duke Charitable Foundation and the V Foundation Rombauer Fellowship; he also receives consulting fees from Guardant Health. Dr. Taylor has disclosed that his work is supported in part by the Prostate Cancer Foundation and the Sontag Foundation. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
Deborah J. Moonan, RN, BSN, Director, Continuing Education, has disclosed that she has no relevant financial relationships.
Ann Gianola, MA, Manager, Continuing Education Accreditation & Program Operations, has disclosed that she has no relevant financial relationships.
Kristina M. Gregory, RN, MSN, OCN, Vice President, Clinical Information Operations, has disclosed that she has no relevant financial relationships.
Rashmi Kumar, PhD, Senior Manager, Clinical Content, has disclosed that she has no relevant financial relationships.
Susan D. Darlow, PhD, Oncology Scientist/Medical Writer, has disclosed that she has no relevant financial relationships.
The authors are grateful to D. Rodriguez-Jaquez for her assistance throughout this work; J. Chmielecki, D. Lipson, and A. Talasaz for data sharing and access; and N. Schultz for critical reading of this manuscript.
Detailed Clinical Timeline.
Compendium of tumors used for comparative genomic analysis. For Figure 2B we used publically available data from 9122 primary tumors to assess the frequency of genetic abnormalities seen in our index case across cancer. Much of these data have been published and abbreviated references are included next to the cohort's name, where available. All cohorts who had at least one tumor with one of our patient's 5 genetic abnormalities (focal genomic amplifications of MYC, CCND3, and SOX2 or mutations in DNMT3A, and BRCA2) were included.
Data from the cBioPortal Web site. Available at: www.cbioportal.org. Accessed June 11, 2014.
McDermott U, Settleman J. Personalized cancer therapy with selective kinase inhibitors: an emerging paradigm in medical oncology. J Clin Oncol 2009;27:5650–5659.
Grilley-Olson JE, Hayes DN, Moore DT et al.. Validation of interobserver agreement in lung cancer assessment: hematoxylin-eosin diagnostic reproducibility for non-small cell lung cancer: the 2004 World Health Organization classification and therapeutically relevant subsets. Arch Pathol Lab Med 2013;137:32–40.
- Search Google Scholar
- Export Citation
. Grilley-Olson JE Hayes DN Moore DT Validation of interobserver agreement in lung cancer assessment: hematoxylin-eosin diagnostic reproducibility for non-small cell lung cancer: the 2004 World Health Organization classification and therapeutically relevant subsets. Arch Pathol Lab Med 2013; 137: 32– 40.
Bolton KL, Chenevix-Trench G, Goh C et al.. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA 2012;307:382–390.
Yang D, Khan S, Sun Y et al.. Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA 2011;306:1557–1565.
Talasaz A, Mortimer S, Sebisanovic D et al.. Use of the GUARDANT360 noninvasive tumor sequencing assay on 300 patients across colorectal, melanoma, lung, breast, and prostate cancers and its clinical utility [abstract]. J Clin Oncol 2014;32(Suppl):Abstract e22041.
- Search Google Scholar
- Export Citation
. Talasaz A Mortimer S Sebisanovic D Use of the GUARDANT360 noninvasive tumor sequencing assay on 300 patients across colorectal, melanoma, lung, breast, and prostate cancers and its clinical utility [abstract]. J Clin Oncol 2014; 32( Suppl): Abstract e22041.
Von Hoff DD, Ervin T, Arena FP et al.. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691–1703.
Frampton GM, Fichtenholtz A, Otto GA et al.. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol 2013;31:1023–1031.
NM_000059.3(BRCA2):c.1813delA (p.Ile605Tyrfs) AND Neoplastic Syndromes, Hereditary - ClinVar - NCBI [Internet]. Available at: http://www.ncbi.nlm.nih.gov/clinvar/RCV000132177.1/. Accessed January 27, 2015.
Landrum MJ, Lee JM, Riley GR et al.. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 2014;42:D980–985.
Biankin AV, Waddell N, Kassahn KS et al.. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 2012;491:399–405.
Waddell N, Pajic M, Patch AM et al.. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 2015;518:495–501.
Alsop K, Fereday S, Meldrum C et al.. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol 2012;30:2654–2663.
Farmer H, McCabe N, Lord CJ et al.. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005;434:917–921.
Tothill RW, Li J, Mileshkin L et al.. Massively-parallel sequencing assists the diagnosis and guided treatment of cancers of unknown primary. J Pathol 2013;231:413–423.
Pleskow DK, Berger HJ, Gyves J et al.. Evaluation of a serologic marker, CA19-9, in the diagnosis of pancreatic cancer. Ann Intern Med 1989;110:704–709.
Greco FA, Lennington WJ, Spigel DR, Hainsworth JD. Molecular profiling diagnosis in unknown primary cancer: accuracy and ability to complement standard pathology. J Natl Cancer Inst 2013;105:782–790.
Tempero MA, Malafa MP, Behrman SW et al.. Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines. J Natl Compr Canc Netw 2014;12:1083–1093.
Conroy T, Desseigne F, Ychou M et al.. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. New Engl J Med 2011;364:1817–1825.
Matsuyama R, Reddy S, Smith TJ. Why do patients choose chemotherapy near the end of life? A review of the perspective of those facing death from cancer. J Clin Oncol 2006;24:3490–3496.
O'Brien ME, Borthwick A, Rigg A et al.. Mortality within 30 days of chemotherapy: a clinical governance benchmarking issue for oncology patients. Br J Cancer 2006;95:1632–1636.
Cerami E, Gao J, Dogrusoz U et al.. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012;2:401–404.
The Cancer Genome Atlas - Cancer Genome - TCGA [Internet]. Available at: http://cancergenome.nih.gov/. Accessed January 27, 2015.
Zhang J, Baran J, Cros A et al.. International Cancer Genome Consortium data portal—a one-stop shop for cancer genomics data. Database (Oxford) 2011;2011:bar026.