Utility of serum DNA as a marker for KRAS mutations in pancreatic cancer tissue

Ako, Soichiro; Nouso, Kazuhiro; Kinugasa, Hideaki; Dohi, Chihiro; Matushita, Hiroshi; Mizukawa, Sho; Muro, Shinichiro; Akimoto, Yutaka; Uchida, Daisuke; Tomoda, Takeshi; Matsumoto, Kazuyuki; Horiguchi, Shigeru; Tsutsumi, Keisuke; Kato, Hironari

doi:10.1016/j.pan.2016.12.011

Cited by 36 publications

(39 citation statements)

References 18 publications

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“…Peripherally detected KRAS mutations are a poor prognostic indicator at all stages of disease [ 64 ]. Mutated KRAS in the peripheral circulation has demonstrated worse OS (3 vs. 11 months in some studies) [ 65 , 66 , 67 , 68 , 69 ].…”

Section: Current Clinical Utility Of Cfdnamentioning

confidence: 99%

Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer

Grunvald

Jacobson

Kuzel

et al. 2020

IJMS

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Pancreatic cancer is a challenging disease with a low 5-year survival rate. There are areas for improvement in the tools used for screening, diagnosis, prognosis, treatment selection, and assessing treatment response. Liquid biopsy, particularly cell free DNA liquid biopsy, has shown promise as an adjunct to our standard care for pancreatic cancer patients, but has not yet been universally adopted into regular use by clinicians. In this publication, we aim to review cfDNA liquid biopsy in pancreatic cancer with an emphasis on current techniques, clinical utility, and areas of active investigation. We feel that researchers and clinicians alike should be familiar with this exciting modality as it gains increasing importance in the care of cancer patients.

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Section: Current Clinical Utility Of Cfdnamentioning

confidence: 99%

Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer

Grunvald

Jacobson

Kuzel

et al. 2020

IJMS

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“…Despite the considerably high sensitivity of digital PCR, the detection of KRAS mutations in plasma using this method has often fallen short of high expectations, as the ctDNA detection rate has averaged as low as 50% 6 , 19 – 21 , 23 . This limitation may be a result of there being low allelic fractions of KRAS mutations in a subset of PDACs 24 .…”

Section: Introductionmentioning

confidence: 99%

Utility of targeted deep sequencing for detecting circulating tumor DNA in pancreatic cancer patients

Park

Son

et al. 2018

Sci Rep

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Targeted deep sequencing across broad genomic regions has been used to detect circulating tumor DNA (ctDNA) in pancreatic ductal adenocarcinoma (PDAC) patients. However, since most PDACs harbor a mutation in KRAS, sequencing of broad regions needs to be systemically compared to analyzing only KRAS mutations for PDAC. Using capture-based targeted deep sequencing, we detected somatic tumor mutations in 17 fine needle aspiration biopsy and 69 longitudinal cell-free DNA (cfDNA) samples from 17 PDAC patients. KRAS mutations were detected in 10 out of 17 pretreatment patient plasma samples. Next, interrogation of genetic alterations in matched primary tumor samples detected ctDNA in 12 of 17 pretreatment plasma samples and cfDNA sequencing across the 83 target genes identified ctDNA in 15 of 17 cases (88.2% sensitivity). This improved sensitivity of ctDNA detection resulted in enhanced tumor burden monitoring when we analyzed longitudinal plasma samples. We found that cfDNA sequencing detected the lowest mutant allelic fractions and number of variants when complete response or partial response to chemotherapy was achieved. We demonstrated that ctDNA levels measured by targeted deep sequencing sensitively indicate the presence of cancer and correlate well with clinical responses to therapy and disease progression in PDAC patients.

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“…It was reported that Kras mutation detected in pancreatic cancer tissues associated with worse disease‐free survival and OS compared with Kras wild‐type tumors. In addition, subtype analysis revealed that patients with Kras G12D mutation had an extremely poor prognosis with a median OS of 15.3 months in resectable pancreatic cancer, while other studies showed different results . Change of Kras mutation in ctDNA could also be used to monitor treatment response in metastatic pancreatic cancer and Kras mutation detected in ctDNA after surgery is associated with early recurrence and metastasis .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, subtype analysis revealed that patients with Kras G12D mutation had an extremely poor prognosis with a median OS of 15.3 months in resectable pancreatic cancer, while other studies showed different results. 22,23 Change of Kras mutation in ctDNA could also be used to monitor treatment response in metastatic pancreatic cancer and Kras mutation detected in ctDNA after surgery is associated with early recurrence and metastasis. 8,24 Two patterns (G12V and G12D) of Kras mutation account for about 90% of all mutations in pancreatic cancer and both mutation rates range from 30% to 50%.…”

Section: Discussionmentioning

confidence: 99%

Kras mutation correlating with circulating regulatory T cells predicts the prognosis of advanced pancreatic cancer patients

Luo

Jin

et al. 2020

Cancer Medicine

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Purpose Kras mutation and abnormal immune status are associated with pancreatic cancer development and progression. In this study, we evaluated the Kras mutation status in circulating tumor DNA and circulating T cell subsets in a cohort of advanced pancreatic cancer patients. Methods Samples were retrospectively obtained from a series of 210 pathological advanced pancreatic cancer patients between 2012 and 2014. The Kras mutation status was detected in cell‐free circulating tumor DNA (ctDNA) by ddPCR and circulating T cell subsets were analyzed by flow cytometry. Results Univariate analysis found that tumor node metastasis (TNM) stage, chemotherapy, circulating regulatory T cells, CA19‐9 levels, CA125 levels, and KrasG12D and KrasG12V mutations were significantly related to overall survival in advanced pancreatic cancer patients. Multivariate analysis identified that TNM stage (P = .03, HR:1.422), Tregs (P = .004, HR:1.522), CA19‐9 levels (P = .009, HR:1.488), KrasG12D mutation (P = .044, HR:1.353), and KrasG12V mutation (P = .001, HR:1.667) were independent prognostic markers. Furthermore, we found that KrasG12V mutation in ctDNA was correlated with high circulating proportion of Tregs, and patients with both KrasG12V mutation and high levels of Tregs were associated with extremely poor survival in advanced pancreatic cancer. Conclusion KrasG12V mutation was associated with high circulating regulatory T cell levels, and both of them predicted worse prognosis in advanced pancreatic cancer patients.

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Utility of serum DNA as a marker for KRAS mutations in pancreatic cancer tissue

Abstract: Serum and plasma were found to be good materials for detecting cancer-specific DNA in the peripheral blood and the presence of KRAS mutations in blood-derived DNA may be used as a prognostic biomarker for patients with pancreatic cancer.

Cited by 36 publications

References 18 publications

Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer

Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer

Utility of targeted deep sequencing for detecting circulating tumor DNA in pancreatic cancer patients

Kras mutation correlating with circulating regulatory T cells predicts the prognosis of advanced pancreatic cancer patients

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