Amplification of mutant KRASG12D in a patient with advanced metastatic pancreatic adenocarcinoma detected by liquid biopsy: A case report

被引：2

作者：

Pittella-Silva, Fabio ^{[1
]}

Kimura, Yasutoshi ^{[2
]}

Low, Siew-Kee ^{[1
]}

Nakamura, Yusuke ^{[1
]}

Motoya, Masayo ^{[3
]}

机构：

[1] Japanese Fdn Canc Res, Canc Precis Med Ctr, Tokyo 1358550, Japan

[2] Sapporo Med Univ, Dept Surg Surg Oncol & Sci, Sch Med, Sapporo, Hokkaido 0608543, Japan

[3] Sapporo Med Univ, Dept Gastroenterol & Hepatol, Sch Med, Sapporo, Hokkaido 0608543, Japan

来源：

MOLECULAR AND CLINICAL ONCOLOGY | 2021年 / 15卷 / 03期

关键词：

case report; diagnosis; KRAS amplification; liquid biopsy; pancreatic ductal adenocarcinoma; prognosis; tumor aggressiveness; CLINICAL-PRACTICE GUIDELINES; ADJUVANT CHEMOTHERAPY; CANCER; GEMCITABINE; RESECTION; TUMOR;

D O I：

10.3892/mco.2021.2334

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancer types. Activating oncogenic KRAS mutations are commonly observed in PDAC; however, oncogenic KRAS amplification is rarely observed, and its significance in prognosis and resistance to therapy remains poorly characterized. The present report describes the case of a 52-year-old male patient diagnosed with advanced PDAC with liver metastasis. The patient received modified FOLFIRINOX (mFFX) therapy to which the patient became intolerant with a strong inflammatory response. Subsequent treatment with gemcitabine plus nab-paclitaxel failed to control the disease. Targeted genetic analysis revealed KRAS(G12D) and TP53(R248Q) mutations in the primary tumor and liver metastases. Analysis of circulating tumor DNA (ctDNA) before the first line of treatment confirmed these genetic findings and revealed a >4-fold amplification of the mutant KRAS(G12D) not detected in the primary tumor. Additionally, subsequent analysis confirmed a 5-fold amplification of the KRAS(G12D) allele in liver metastasis. Consecutive monitoring of ctDNA revealed an initial decrease in the tumor burden 2 weeks after the first cycle of mFFX. However, coinciding with treatment intolerance, a sharp increase in tumor mutational levels and KRAS(G12D) amplification was observed 1 month later. The patient died 70 days after treatment initiation. Overall, amplification of oncogenic KRAS(G12D) was not only associated with an aggressive phenotype, but also supported cancer resistance to chemotherapy. Importantly, this case suggests that plasma detection of KRAS(G12D) amplification is feasible in the clinical routine and constitutes a powerful tool for assessing tumor aggressiveness.

引用

页数：5

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