Seok Jin Kim, Yeon Jeong Kim, Sang Eun Yoon, Kyung Ju Ryu, Bon Park, Donghyun Park, Duck Cho, Hyun-Young Kim, Junhun Cho, Young Hyeh Ko, Woong-Yang Park, Won Seog Kim
Cancer Res Treat. 2023;55(1):291-303. Published online March 2, 2022
Purpose Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL).
Materials and Methods After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes.
Results Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE.
Conclusion Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.
Citations
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Cancer Res Treat. 2022;54(2):597-612. Published online July 23, 2021
Purpose
Analysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL.
Materials and Methods
Targeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018.
Results
Targeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment.
Conclusion
The plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.
Citations
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This report represents a clinical study of 50 cases of hepatocellular carcinoma diagnosed at the Dept. of Internal Medicine of CMC Kangnam St. Marys Hoapital from 1981 Mar. to 1985 Mar. The results are as follows: 1) The peak incidence of age is the 6 th decade and the ratio of male to female is 12, 2) The combination with cirrhosis is found in 68.2% and hepatomegaly is palpated in 94%. 3) In laboratory data, positive antigen in 68.3%, the elevation of GPT is 2.17. alpha-fetoprotein is noted in 62.5%, positive Australia alkaline phosphatase in 85.7% and the ratio of GOT to 4) The accuracy of each imaging findings in diagnosis of hepatocellular carcinoma was that scintigraphy was in 84%, and both ultrasonography and computerized tomography were more accurate than scintigraphy.