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The Evolutionary Origins of Recurrent Pancreatic Cancer.
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.
Afiliación
  • Sakamoto H; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Attiyeh MA; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Gerold JM; Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts.
  • Makohon-Moore AP; Department of Mathematics and Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts.
  • Hayashi A; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Hong J; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Kappagantula R; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Zhang L; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Melchor JP; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Reiter JG; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Heyde A; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Bielski CM; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Penson AV; Canary Center for Cancer Early Detection, Department of Radiology, Stanford University, Palo Alto, California.
  • Gönen M; Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts.
  • Chakravarty D; Department of Mathematics and Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts.
  • O'Reilly EM; Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Wood LD; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Hruban RH; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Nowak MA; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Socci ND; Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Taylor BS; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Iacobuzio-Donahue CA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Cancer Discov ; 10(6): 792-805, 2020 06.
Article en En | MEDLINE | ID: mdl-32193223
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.See related commentary by Bednar and Pasca di Magliano, p. 762.This article is highlighted in the In This Issue feature, p. 747.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Metástasis de la Neoplasia / Recurrencia Local de Neoplasia Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cancer Discov Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Metástasis de la Neoplasia / Recurrencia Local de Neoplasia Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cancer Discov Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos