scholarly journals Effects of Co-occurring Genomic Alterations on Survival in Patients with KRAS-Mutant Pancreatic Cancer

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Moon Kangeun ◽  
Jae Kim Min ◽  
Chang Hyeonmin ◽  
Dongmyung Oh
Keyword(s):  
Pancreatic Cancer ◽  
Genomic Alterations

scholarly journals Identification of genomic alterations and associated transcriptomic profiling reveal the prognostic significance of MMP14 and PKM2 in patients with pancreatic cancer

Aging ◽  
2020 ◽  
Vol 12 (18) ◽  
pp. 18676-18692
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Yingying Lin ◽  
Ji Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Prognostic Significance ◽  
Genomic Alterations ◽  
Transcriptomic Profiling

The landscape of POLE/POLD1 mutations in Chinese solid tumor patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13050-e13050 ◽  
Author(s):  
Linrong Pang ◽  
Tao Xu ◽  
Hua Tao ◽  
Gang Chen ◽  
Bin Ni ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Endometrial Cancer ◽  
Solid Tumors ◽  
Urothelial Cancer ◽  
Somatic Mutations ◽  
Checkpoint Inhibitors ◽  
Chinese Patients ◽  
Unknown Primary ◽  
Cancer Genes ◽  
Genomic Alterations

e13050 Background: DNA polymerase epsilon and polymerase delta encoded by the POLE and POLD1 gene are the major components participating in DNA replication, which both carry a proofreading (exonuclease) domain allowing error correction during replication. In case of POLE/POLD1 mutation, a deficient DNA repair activity results in a hypermutated phenotype of cancer, which would be a promising biomarker for immune checkpoint inhibitors (ICPIs). However, the prevalence of POLE and POLD1 in Chinese patients (pts) with solid tumors remained unknown. Methods: Targeted panel sequencing of 450 cancer genes were performed on FFPE tissues and matched blood samples obtained from 6313 Chinese pts with 23 different types of solid tumors. In our cohort, 41% were female pts with a median age of 56-year-old (range: 1-91), while 59% were male with a median age of 59-year-old (range: 1-96). The major cancer types were NSCLC (29%), HCC (11%), CRC (11%), gastric cancer (GC, 7%), soft tissure sarcoma (6%), pancreatic cancer (5%), intrahepatic cholangiocarcinoma (5%), and others. Somatic genomic alterations (sGAs) including single base substitutions, short and long insertions/deletions (indels), copy number alterations (CNA), rearrangements, TMB and MSI status were assessed by NGS. Results: Clinical relevant genomic alterations (CRGAs) were defined as known loss-of-function mutations, truncations, mutations on splicing sites and confirmed somatic mutations in COSMIC. CRGAs of POLE and POLD1 accounted for 2.1% and 1.3% of Chinese solid tumors respectively. Tumors with highest frequency of POLE CRGAs in Chinese cohort were endometrial cancer (8.3%), urothelial cancer (4.8%), CRC (4.3%), GC (3.2%), breast cancer (2.9%), cancer of unknown primary (CUP, 2.5%), ovarian cancer (2.1%) and NSCLC (2.0%), which tumors with highest frequency of POLD1 CRGAs were endometrial cancer (8.3%), urothelial cancer (4.8%), GC (3.0%), CRC (2.8%), SCLC (2.1%), HCC (1.9%), cervical cancer (1.6%), CUP (1.2%) and pancreatic cancer (1.2%). In addition, 1.6% and 1.2% of Chinese solid tumors harbored variants of unknown significance of POLE and POLD1, respectively. Conclusions: For the first time, our study reported prevalence of somatic mutations of POLE and POLD1 in large samples of Chinese population. Comparing with large cohort study of western population (ESMO 2017, 1170P), more CRGAs of POLE were identified in Chinese solid tumors (2.1% vs. 0.6%, p < 0.0001) indicating ethnic differences of ICPIs potential candidates between Chinese and western populations.

Circulating cell free tumor DNA detection as a prognostic tool in advanced pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4130-4130
Author(s):  
Gehan Botrus ◽  
Pedro Luiz Serrano Uson Junior ◽  
Puneet Raman ◽  
Adrienne Kaufman ◽  
Heidi E. Kosiorek ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Systemic Treatment ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Genetic Alterations ◽  
Genomic Alterations ◽  
Systemic Treatments ◽  
Investigation Methods ◽  
The Impact ◽  
Tumor Dna

4130 Background: Circulating cell-free tumor DNA (ctDNA) genomic profiling is an emerging tool for pancreatic cancer. The impact of detected genomic alterations in tumor response to systemic treatments and outcomes is under investigation. Methods: Patients with advanced pancreatic cancer and ctDNA collected at time of initial diagnosis were retrospectively evaluated. Results of ctDNA analysis were correlated with patients’ demographics, systemic treatment response, progression-free survival (PFS) and overall survival (OS). Results: A total of 104 patients were included in the analysis. The mean age was 70.5 years (SD: 8.3), 50% were male, 37% with locally advanced disease and 63% with metastatic disease. Somatic alterations were detected in 84.6 % of the patients, no genetic alterations were detected in 15.4%, and were associated more with locally advanced pancreatic cancer as opposed to metastatic, p = 0.025. 60.6 % of the cohort had ≥ 2 genomic alterations detected. 28% were treated with FOLFIRINOX and 63% with gemcitabine plus nab-paclitaxel as first-line systemic treatment. Patients with any detectable genomic alterations when compared to patients with no detectable variant had worse median PFS (6.2 versus 15.3 months, p = 0.005) and patients with ≥ 2 detectable genomic alterations had worse median PFS (5.6 versus 11.0 months, p < 0.001) and worse median OS (11.5 versus 24.2 months, p = 0.001). KRAS was detected in 62.5% of the patients and was associated with PD to systemic treatments (80.4% vs 19.6%, p = 0.006), worse median PFS (5.8 versus 13.0 months, p < 0.001) and worse median OS (11.5 versus 26.3 months, p = 0.002). TP53 was detected in 60% of patients and was associated with worse median PFS (5.9 versus 10.9 months, p = 0.02) and worse median OS (13.5 versus 24.2 months, p = 0.001). CCND2 was detected in 14% of the patients and was associated with worse median PFS (3.6 versus 8.2 months, p = 0.004). Conclusions: Our study showed that initial detection of ctDNA may identify different genomic alterations that help predict disease outcomes, confirmation of these findings in larger studies are warranted.

scholarly journals Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Mark Sausen ◽  
Jillian Phallen ◽  
Vilmos Adleff ◽  
Siân Jones ◽  
Rebecca J. Leary ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Clinical Implications ◽  
Genomic Alterations
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