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Sakamoto, Hitomi; Attiyeh, Marc A; Gerold, Jeffrey M; Makohon-Moore, Alvin P; Hayashi, Akimasa; Hong, Jungeui; Kappagantula, Rajya; Zhang, Lance; Melchor, Jerry P; Reiter, Johannes G; Heyde, Alexander; Bielski, Craig M; Penson, Alexander V; Gönen, Mithat; Chakravarty, Debyani; O'Reilly, Eileen M; Wood, Laura D; Hruban, Ralph H; Nowak, Martin A; Socci, Nicholas D; Taylor, Barry S; Iacobuzio-Donahue, Christine A
Cancer discovery, 06/2020, Letnik: 10, Številka: 6Journal Article
Surgery is the only curative option for stage I/II pancreatic cancer; nonetheless, most patients will experience a recurrence after surgery and die of their disease. To identify novel opportunities for management of recurrent pancreatic cancer, we performed whole-exome or targeted sequencing of 10 resected primary cancers and matched intrapancreatic recurrences or distant metastases. We identified that recurrent disease after adjuvant or first-line platinum therapy corresponds to an increased mutational burden. Recurrent disease is enriched for genetic alterations predicted to activate MAPK/ERK and PI3K-AKT signaling and develops from a monophyletic or polyphyletic origin. Treatment-induced genetic bottlenecks lead to a modified genetic landscape and subclonal heterogeneity for driver gene alterations in part due to intermetastatic seeding. In 1 patient what was believed to be recurrent disease was an independent (second) primary tumor. These findings suggest routine post-treatment sampling may have value in the management of recurrent pancreatic cancer. SIGNIFICANCE: The biological features or clinical vulnerabilities of recurrent pancreatic cancer after pancreaticoduodenectomy are unknown. Using whole-exome sequencing we find that recurrent disease has a distinct genomic landscape, intermetastatic genetic heterogeneity, diverse clonal origins, and higher mutational burden than found for treatment-naïve disease. . .
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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