Correction: Earl et al. Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival. Cancers 2021, 13, 1612

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10–15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.

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Characterization of the germline and somatic mutation profile in familial pancreatic cancer reveals pathogenic germline variants and potentially druggable somatic mutations.

Pancreatology ◽

10.1016/j.pan.2020.07.188 ◽

2020 ◽

Vol 20 ◽

pp. S108

Author(s):

J. Earl ◽

M. Castillo ◽

E. Barreto ◽

M. Rodríguez-Garrote ◽

V. Pachón ◽

...

Keyword(s):

Pancreatic Cancer ◽

Somatic Mutation ◽

Somatic Mutations ◽

Familial Pancreatic Cancer ◽

Germline Variants ◽

Mutation Profile

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KRAS negativity and a longer overall survival in hereditary and familial pancreatic cancer cases

Pancreatology ◽

10.1016/j.pan.2021.05.234 ◽

2021 ◽

Vol 21 ◽

pp. S86-S87

Author(s):

J. Earl ◽

E. Barreto ◽

M.E. Castillo ◽

R. Fuentes ◽

M. Rodriguez-Garrote ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Familial Pancreatic Cancer

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Long non-coding RNA PART1 predicts a poor prognosis and promotes the malignant progression of pancreatic cancer by sponging miR-122

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02232-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xibao Hu ◽

Lei Zhang ◽

Jingjing Tian ◽

Junhong Ma

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Overall Survival ◽

Clinical Stage ◽

Malignant Progression ◽

Luciferase Reporter ◽

Poor Overall Survival ◽

Pancreatic Cancer Cells ◽

Non Coding Rna ◽

Long Non Coding Rna

Abstract Background and objectives Long non-coding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) was previously shown to exert an oncogenic role in several human cancers. However, whether PART1 is associated with the malignant progression of pancreatic cancer remains unclear. In the current study, we aimed to identify the role and potential mechanism of PART1 in pancreatic cancer. Methods qRT-PCR was applied to detect PART1 expression in 45 cases of pancreatic cancer patients. The chi-square test was performed to assess the association between PART1 expression and clinicopathologic features, and Kaplan-Meier method was applied to evaluate overall survival. In vitro CCK-8, transwell invasion, and flow cytometry assays were applied to detect the effects of PART1 on cell proliferation, invasion, and apoptosis, respectively. Luciferase reporter and RNA immunoprecipitation assays were used to identify the regulatory mechanism between PART1 and miR-122. Results PART1 expression was upregulated in pancreatic cancer tissues and cell lines. High PART1 expression was closely correlated with tumor size, T classification, clinical stage, and vascular invasion, and predicted a poor overall survival. PART1 knockdown significantly suppressed cell proliferation and invasion abilities of pancreatic cancer but promoted cell apoptosis. PART1 was found to serve as a molecular sponge of miR-122, and miR-122 inhibition partially reversed the inhibitory phenotypes of PART1 knockdown on pancreatic cancer cells. Conclusions PART1 promotes the malignant progression of pancreatic cancer by sponging miR-122. The PART1/miR-122 axis might be a promising target for anticancer therapy in patients with pancreatic cancer.

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Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS

Nature Communications ◽

10.1038/s41467-021-24109-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

A. Rose Brannon ◽

Gowtham Jayakumaran ◽

Monica Diosdado ◽

Juber Patel ◽

Anna Razumova ◽

...

Keyword(s):

Cancer Patients ◽

De Novo ◽

Low Frequency ◽

High Sensitivity ◽

Clinical Analysis ◽

De Novo Mutation ◽

Cell Free Dna ◽

Free Dna ◽

Somatic Alterations ◽

Mutation Profiling

AbstractCirculating cell-free DNA from blood plasma of cancer patients can be used to non-invasively interrogate somatic tumor alterations. Here we develop MSK-ACCESS (Memorial Sloan Kettering - Analysis of Circulating cfDNA to Examine Somatic Status), an NGS assay for detection of very low frequency somatic alterations in 129 genes. Analytical validation demonstrated 92% sensitivity in de-novo mutation calling down to 0.5% allele frequency and 99% for a priori mutation profiling. To evaluate the performance of MSK-ACCESS, we report results from 681 prospective blood samples that underwent clinical analysis to guide patient management. Somatic alterations are detected in 73% of the samples, 56% of which have clinically actionable alterations. The utilization of matched normal sequencing allows retention of somatic alterations while removing over 10,000 germline and clonal hematopoiesis variants. Our experience illustrates the importance of analyzing matched normal samples when interpreting cfDNA results and highlights the importance of cfDNA as a genomic profiling source for cancer patients.

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Induction Chemotherapy for Primarily Unresectable Locally Advanced Pancreatic Adenocarcinoma—Who Will Benefit from a Secondary Resection?

Medicina ◽

10.3390/medicina57010077 ◽

2021 ◽

Vol 57 (1) ◽

pp. 77

Author(s):

Nathalie Rosumeck ◽

Lea Timmermann ◽

Fritz Klein ◽

Marcus Bahra ◽

Sebastian Stintzig ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Neoadjuvant Therapy ◽

Induction Therapy ◽

Locally Advanced ◽

Eastern Cooperative Oncology Group ◽

Advanced Pancreatic Cancer ◽

Comprehensive Cancer Center ◽

Secondary Resection ◽

Number Of Patients

Background and Objectives: An increasing number of patients (pts) with locally advanced pancreatic cancer (LAPC) are treated with an intensive neoadjuvant therapy to obtain a secondary curative resection. Only a certain number of patients benefit from this intention. The aim of this investigation was to identify prognostic factors which may predict a benefit for secondary resection. Materials and Methods: Survival time and clinicopathological data of pts with pancreatic cancer were prospective and consecutively collected in our Comprehensive Cancer Center Database. For this investigation, we screened for pts with primarily unresectable pancreatic cancer who underwent a secondary resection after receiving induction therapy in the time between March 2017 and May 2019. Results: 40 pts had a sufficient database to carry out a reliable analysis. The carbohydrate-antigen 19-9 (CA 19-9) level of the pts treated with induction therapy decreased by 44.7% from 4358.3 U/mL to 138.5 U/mL (p = 0.001). The local cancer extension was significantly reduced (p < 0.001), and the Eastern Cooperative Oncology Group (ECOG) performance status was lowered (p = 0.03). The median overall survival (mOS) was 20 months (95% CI: 17.2–22.9). Pts who showed a normal CA 19-9 level (<37 U/mL) at diagnosis and after neoadjuvant therapy or had a Body Mass Index (BMI) below 25 kg/m2 after chemotherapy had a significant prolonged overall survival (29 vs. 19 months, p = 0.02; 26 vs. 18 months, p = 0.04; 15 vs. 24 months, p = 0.01). Pts who still presented elevated CA 19-9 levels >400 U/mL after induction therapy did not profit from a secondary resection (24 vs. 7 months, p < 0.001). Nodal negativity as well as the performance of an adjuvant therapy lead to better mOS (25 vs. 15 months, p = 0.003; 10 vs. 25 months, p < 0.001). Conclusion: The pts in our investigation had different benefits from the multimodal treatment. We identified the CA 19-9 level at time of diagnosis and after neoadjuvant therapy as well as the preoperative BMI as predictive factors for overall survival. Furthermore, diagnostics of presurgical nodal status should gain more importance as nodal negativity is associated with better outcome.

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Liquid Biopsy in Pancreatic Cancer: Are We Ready to Apply It in the Clinical Practice?

Cancers ◽

10.3390/cancers13081986 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1986

Author(s):

Victoria Heredia-Soto ◽

Nuria Rodríguez-Salas ◽

Jaime Feliu

Keyword(s):

Pancreatic Cancer ◽

Clinical Practice ◽

Early Diagnosis ◽

Minimally Invasive ◽

Liquid Biopsy ◽

Genetic Material ◽

Current Status ◽

Ductal Adenocarcinoma ◽

Disease Monitoring ◽

Global Status

Pancreatic ductal adenocarcinoma (PDAC) exhibits the poorest prognosis of all solid tumors, with a 5-year survival of less than 10%. To improve the prognosis, it is necessary to advance in the development of tools that help us in the early diagnosis, treatment selection, disease monitoring, evaluation of the response and prognosis. Liquid biopsy (LB), in its different modalities, represents a particularly interesting tool for these purposes, since it is a minimally invasive and risk-free procedure that can detect both the presence of genetic material from the tumor and circulating tumor cells (CTCs) in the blood and therefore distantly reflect the global status of the disease. In this work we review the current status of the main LB modalities (ctDNA, exosomes, CTCs and cfRNAs) for detecting and monitoring PDAC.

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