Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer

article Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer published yes Alvin Makohon Moore author Ming Zhang author Johannes Reiter author 4A918E98-F248-11E8-B48F-1D18A9856A870000-0002-0170-7353 Ivana Božić author Benjamin Allen author Deepanjan Kundu author 1d4c0f4f-e8a3-11ec-a351-e36772758c45 Krishnendu Chatterjee author 2E5DCA20-F248-11E8-B48F-1D18A9856A870000-0002-4561-241X Fay Wong author Yuchen Jiao author Zachary Kohutek author Jungeui Hong author Marc Attiyeh author Breanna Javier author Laura Wood author Ralph Hruban author Martin Nowak author Nickolas Papadopoulos author Kenneth Kinzler author Bert Vogelstein author Christine Iacobuzio Donahue author KrCh department Quantitative Graph Games: Theory and Applications project Modern Graph Algorithmic Techniques in Formal Verification project Game Theory project 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. https://research-explorer.ista.ac.at/download/653/7050/2017_NatureGenetics_Makohon.pdf application/pdfno Nature Publishing Group2017 eng Nature Genetics 1061-4036 28092682 00039491780000910.1038/ng.3764 493358 - 366 A. Makohon Moore et al., “Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer,” Nature Genetics, vol. 49, no. 3. Nature Publishing Group, pp. 358–366, 2017. Makohon Moore A, Zhang M, Reiter J, et al. Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer. Nature Genetics. 2017;49(3):358-366. doi:<a href="https://doi.org/10.1038/ng.3764">10.1038/ng.3764</a> Makohon Moore, A., Zhang, M., Reiter, J., Božić, I., Allen, B., Kundu, D., … Iacobuzio Donahue, C. (2017). Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer. Nature Genetics. Nature Publishing Group. <a href="https://doi.org/10.1038/ng.3764">https://doi.org/10.1038/ng.3764</a> Makohon Moore A, Zhang M, Reiter J, Božić I, Allen B, Kundu D, Chatterjee K, Wong F, Jiao Y, Kohutek Z, Hong J, Attiyeh M, Javier B, Wood L, Hruban R, Nowak M, Papadopoulos N, Kinzler K, Vogelstein B, Iacobuzio Donahue C. 2017. Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer. Nature Genetics. 49(3), 358–366. A. Makohon Moore, M. Zhang, J. Reiter, I. Božić, B. Allen, D. Kundu, K. Chatterjee, F. Wong, Y. Jiao, Z. Kohutek, J. Hong, M. Attiyeh, B. Javier, L. Wood, R. Hruban, M. Nowak, N. Papadopoulos, K. Kinzler, B. Vogelstein, C. Iacobuzio Donahue, Nature Genetics 49 (2017) 358–366. Makohon Moore, Alvin, et al. “Limited Heterogeneity of Known Driver Gene Mutations among the Metastases of Individual Patients with Pancreatic Cancer.” Nature Genetics, vol. 49, no. 3, Nature Publishing Group, 2017, pp. 358–66, doi:<a href="https://doi.org/10.1038/ng.3764">10.1038/ng.3764</a>. Makohon Moore, Alvin, Ming Zhang, Johannes Reiter, Ivana Božić, Benjamin Allen, Deepanjan Kundu, Krishnendu Chatterjee, et al. “Limited Heterogeneity of Known Driver Gene Mutations among the Metastases of Individual Patients with Pancreatic Cancer.” Nature Genetics. Nature Publishing Group, 2017. <a href="https://doi.org/10.1038/ng.3764">https://doi.org/10.1038/ng.3764</a>. 6532018-12-11T11:47:43Z2025-09-11T07:12:56Z