Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer
Open accessAbstract
The extent of heterogeneity among driver gene mutations present in naturally occurring metastases-that is, treatment-naive metastatic disease-is largely unknown. To address this issue, we carried out 60× whole-genome sequencing of 26 metastases from four patients with pancreatic cancer. We found that identical mutations in known driver genes were present in every metastatic lesion for each patient studied. Passenger gene mutations, which do not have known or predicted functional consequences, accounted for all intratumoral heterogeneity. Even with respect to these passenger mutations, our analysis suggests that the genetic similarity among the founding cells of metastases was higher than that expected for any two cells randomly taken from a normal tissue. The uniformity of known driver gene mutations among metastases in the same patient has critical and encouraging implications for the success of future targeted therapies in advanced-stage disease.
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Stage-matched PDAC long-term survivors do not show significant genomic differences compared with shorter-survival patients.
“analysis of stage-matched PDAC long term survivors has not demonstrated significant genomic differences compared to those patients with shorter survival”
From Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes (2019) · cites this paper as Makohon-Moore et al., 2017
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- Authors
- Makohon-Moore, A. P., Zhang, M., Reiter, J. G., Bozic, I., Allen, B., Kundu, D., Chatterjee, K., Wong, F., Jiao, Y., Kohutek, Z. A., Hong, J., Attiyeh, M., Javier, B., Wood, L. D., Hruban, R. H., Nowak, M. A., Papadopoulos, N., Kinzler, K. W., Vogelstein, B., & Iacobuzio-Donahue, C. A.
- Affiliations
- Johns Hopkins University (US)
- Harvard University (US)
- Institute of Science and Technology Austria (AT)
- Memorial Sloan Kettering Cancer Center (US)
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Nature Genetics
- Published
- 2017-01-16
- Volume
- 49
- Issue
- 3
- Pages
- 358-366
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC5663439
- OpenAlex
- W2576896693
- Cited by
- 403
- References
- 63
- Citations by year
- 2026: 17 · 2025: 35 · 2024: 34 · 2023: 38 · 2022: 37 · 2021: 54 · 2020: 55 · 2019: 33 · 2018: 62 · 2017: 37
- FWCI
- 17.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Memorial Sloan-Kettering Cancer Center
- National Cancer Institute (T32CA160001, R01CA179991, F31CA180682, R37CA043460, P50CA062924, P30CA008748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- pancreatic cancer, metastasis, intratumoral heterogeneity, driver mutations, passenger mutations, clonal evolution, primary tumor, targeted therapy, cancer genomics
- MeSH terms
- Humans, Mutation, Neoplasm Metastasis, Pancreatic Neoplasms
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