Somatic mutations in exocrine pancreatic tumors: association with patient survival.
KRAS mutations are major factors involved in initiation and maintenance of pancreatic tumors. The impact of different mutations on patient survival has not been clearly defined. We screened tumors from 171 pancreatic cancer patients for mutations in KRAS and CDKN2A genes. Mutations in KRAS were dete...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0060870&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850138169832374272 |
|---|---|
| author | P Sivaramakrishna Rachakonda Andrea S Bauer Huaping Xie Daniele Campa Cosmeri Rizzato Federico Canzian Stefania Beghelli William Greenhalf Eithne Costello Michaela Schanne Anette Heller Aldo Scarpa John P Neoptolemos Jens Werner Markus Büchler Jörg D Hoheisel Kari Hemminki Nathalia Giese Rajiv Kumar |
| author_facet | P Sivaramakrishna Rachakonda Andrea S Bauer Huaping Xie Daniele Campa Cosmeri Rizzato Federico Canzian Stefania Beghelli William Greenhalf Eithne Costello Michaela Schanne Anette Heller Aldo Scarpa John P Neoptolemos Jens Werner Markus Büchler Jörg D Hoheisel Kari Hemminki Nathalia Giese Rajiv Kumar |
| author_sort | P Sivaramakrishna Rachakonda |
| collection | DOAJ |
| description | KRAS mutations are major factors involved in initiation and maintenance of pancreatic tumors. The impact of different mutations on patient survival has not been clearly defined. We screened tumors from 171 pancreatic cancer patients for mutations in KRAS and CDKN2A genes. Mutations in KRAS were detected in 134 tumors, with 131 in codon 12 and only 3 in codon 61. The GGT>GAT (G12D) was the most frequent mutation and was present in 60% (80/134). Deletions and mutations in CDKN2A were detected in 43 tumors. Analysis showed that KRAS mutations were associated with reduced patient survival in both malignant exocrine and ductal adenocarcinomas (PDAC). Patients with PDACs that had KRAS mutations showed a median survival of 17 months compared to 30 months for those without mutations (log-rank P = 0.07) with a multivariate hazard ratio (HR) of 2.19 (95%CI 1.09-4.42). The patients with G12D mutation showed a median survival of 16 months (log-rank-test P = 0.03) and an associated multivariate HR 2.42 (95%CI 1.14-2.67). Although, the association of survival in PDAC patients with CDKN2A aberrations in tumors was not statistically significant, the sub-group of patients with concomitant KRAS mutations and CDKN2A alterations in tumors were associated with a median survival of 13.5 months compared to 22 months without mutation (log-rank-test P = 0.02) and a corresponding HR of 3.07 (95%CI 1.33-7.10). Our results are indicative of an association between mutational status and survival in PDAC patients, which if confirmed in subsequent studies can have potential clinical application. |
| format | Article |
| id | doaj-art-c15defcb1b3b44cb9aebfc5a3add6314 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-c15defcb1b3b44cb9aebfc5a3add63142025-08-20T02:30:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6087010.1371/journal.pone.0060870Somatic mutations in exocrine pancreatic tumors: association with patient survival.P Sivaramakrishna RachakondaAndrea S BauerHuaping XieDaniele CampaCosmeri RizzatoFederico CanzianStefania BeghelliWilliam GreenhalfEithne CostelloMichaela SchanneAnette HellerAldo ScarpaJohn P NeoptolemosJens WernerMarkus BüchlerJörg D HoheiselKari HemminkiNathalia GieseRajiv KumarKRAS mutations are major factors involved in initiation and maintenance of pancreatic tumors. The impact of different mutations on patient survival has not been clearly defined. We screened tumors from 171 pancreatic cancer patients for mutations in KRAS and CDKN2A genes. Mutations in KRAS were detected in 134 tumors, with 131 in codon 12 and only 3 in codon 61. The GGT>GAT (G12D) was the most frequent mutation and was present in 60% (80/134). Deletions and mutations in CDKN2A were detected in 43 tumors. Analysis showed that KRAS mutations were associated with reduced patient survival in both malignant exocrine and ductal adenocarcinomas (PDAC). Patients with PDACs that had KRAS mutations showed a median survival of 17 months compared to 30 months for those without mutations (log-rank P = 0.07) with a multivariate hazard ratio (HR) of 2.19 (95%CI 1.09-4.42). The patients with G12D mutation showed a median survival of 16 months (log-rank-test P = 0.03) and an associated multivariate HR 2.42 (95%CI 1.14-2.67). Although, the association of survival in PDAC patients with CDKN2A aberrations in tumors was not statistically significant, the sub-group of patients with concomitant KRAS mutations and CDKN2A alterations in tumors were associated with a median survival of 13.5 months compared to 22 months without mutation (log-rank-test P = 0.02) and a corresponding HR of 3.07 (95%CI 1.33-7.10). Our results are indicative of an association between mutational status and survival in PDAC patients, which if confirmed in subsequent studies can have potential clinical application.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0060870&type=printable |
| spellingShingle | P Sivaramakrishna Rachakonda Andrea S Bauer Huaping Xie Daniele Campa Cosmeri Rizzato Federico Canzian Stefania Beghelli William Greenhalf Eithne Costello Michaela Schanne Anette Heller Aldo Scarpa John P Neoptolemos Jens Werner Markus Büchler Jörg D Hoheisel Kari Hemminki Nathalia Giese Rajiv Kumar Somatic mutations in exocrine pancreatic tumors: association with patient survival. PLoS ONE |
| title | Somatic mutations in exocrine pancreatic tumors: association with patient survival. |
| title_full | Somatic mutations in exocrine pancreatic tumors: association with patient survival. |
| title_fullStr | Somatic mutations in exocrine pancreatic tumors: association with patient survival. |
| title_full_unstemmed | Somatic mutations in exocrine pancreatic tumors: association with patient survival. |
| title_short | Somatic mutations in exocrine pancreatic tumors: association with patient survival. |
| title_sort | somatic mutations in exocrine pancreatic tumors association with patient survival |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0060870&type=printable |
| work_keys_str_mv | AT psivaramakrishnarachakonda somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT andreasbauer somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT huapingxie somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT danielecampa somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT cosmeririzzato somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT federicocanzian somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT stefaniabeghelli somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT williamgreenhalf somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT eithnecostello somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT michaelaschanne somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT anetteheller somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT aldoscarpa somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT johnpneoptolemos somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT jenswerner somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT markusbuchler somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT jorgdhoheisel somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT karihemminki somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT nathaliagiese somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival AT rajivkumar somaticmutationsinexocrinepancreatictumorsassociationwithpatientsurvival |