The GIST and Sarcoma Journal ���� NF1, a tumor suppressor that functions as a negative regulator of the Ras pathway, is among the most frequently mutated genes in several subtypes of sarcomas. Germline and somatic loss of NF1 in neurofibromatosis patients cause malignant peripheral nerve sheath tumors and GISTs. In addition, somatic NF1 mutations, including deletions, have been reported in a wide variety of pediatric and adult softtissue sarcomas with complex karyotypes . Although no therapeutics that target KRAS or NF1 are available, our study shows that repeated sampling using liquid biopsies opens new possibilities to identify and monitor biomarkers that can be used in targeted therapies. The allele frequencies of the six mutated genes in the cfDNA represent the ctDNA level during disease progression. Three days after surgery, ctDNA was still detectable in the liquid biopsy. cfDNA has a rapid clearance, with reported half-life from 15 min to 13 h for fetal cfDNA in plasma. Although not detectable by CT before surgery, metastatic disease was detected in two lymph nodes removed during the hemipelvectomy, and a small amount of ctDNA detected was likely released from additional undiscovered local metastases that could not be detected by conventional diagnostic modalities. The patient had a very aggressive course of the disease, and metastases were detected both in soft tissue, skeleton and lungs only a few weeks after surgery. The plasma collected six weeks after surgery showed an increase in ctDNA relative to the levels before surgery, reflecting the presence of a tumor and rapid disease progression. The cfDNA can originate from both normal and tumour cells. Based on the high mutated allele frequencies determined in plasma, the initial level of cfDNA is dominated by DNA from the tumor. Most of the cfDNA present three days after surgery is believed to originate from tissue injury and inflammation of normal cells as a consequence of the extensive surgery, which would explain the apparently higher normal contribution to the cfDNA at this time point. After six weeks, there was a large increase in cfDNA accompanied with an increase of the mutated allele frequencies. Thus, the quantities of cfDNA present in the plasma reflected the clinical status of the patient due to the fact that most of the cfDNA released during disease progression was tumour derived. Conclusion This study is the first report of using targeted resequencing of cfDNA from serial plasma samples to monitor disease progression in a soft tissue sarcoma patient. The findings show that the level of tumour-specific mutations in liquid biopsies is correlated to disease course in sarcomas, including clinical manifestation of metastatic disease. 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