Mengjie Xu, David S Tourigny, Juliane Lippert, Ana Crastin, Silke Appenzeller, Miriam Asia, Oskar Podstawka, Gabrielle Smith, Yasir S Elhassan, Kassiani Skordilis, Alessandro Prete, Cristina L Ronchi
{"title":"肾上腺皮质腺瘤的ccfDNA分型分析。","authors":"Mengjie Xu, David S Tourigny, Juliane Lippert, Ana Crastin, Silke Appenzeller, Miriam Asia, Oskar Podstawka, Gabrielle Smith, Yasir S Elhassan, Kassiani Skordilis, Alessandro Prete, Cristina L Ronchi","doi":"10.1007/s40618-025-02540-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Somatic alterations are commonly observed in adrenocortical adenomas including cortisol-producing (CPA) [overt Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS)], aldosterone-producing (APA), and non-functioning (NFAT) tumors. We tested whether somatic variants could be detected in circulating cell-free DNA (ccfDNA) from patients with adenomas and potentially contribute to management strategies.</p><p><strong>Materials and methods: </strong>We investigated 44 patients (17 CPA-MACS, 9 CPA-CS, 12 APA, and 6 NFAT). 23 healthy subjects (HS) served as controls. ccfDNA was extracted from blood samples and quantified with fluorimeter. Tumor DNA (T-DNA) was isolated from paraffin embedded tissue in 17/44 cases. Matched ccfDNA/T-DNA were sequenced using a customized panel including 32 genes. Leucocyte DNA was used to filter out germline variants.</p><p><strong>Results: </strong>Patients with adenomas had higher total ccfDNA concentrations than HS [median 0.12 (IQR 0.05-0.19) vs. 0.05 (0.00-0.08) ng/µl, P < 0.001], with CPA-CS showing the highest ccfDNA levels [0.18 (0.05-0.47) ng/µl]. Within T-DNA, somatic variants were identified in 53% of adenomas: PRKACA in 2/7 CPA-CS, CTNNB1 in 3/5 CPA-MACS and 1/7 CPA-CS, KCNJ5 in 2/5 APA and CACNA1D in 1/5 APA. Somatic mutations were not detected in any of the investigated ccfDNA samples.</p><p><strong>Conclusions: </strong>Total ccfDNA concentrations are higher in patients with CPA-CS. Despite the presence of somatic variants in half of tumor samples, we did not detect any at ccfDNA level. Therefore, this approach appears ineffective for pre-operative detection of genetic alterations.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1207-1216"},"PeriodicalIF":5.4000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049379/pdf/","citationCount":"0","resultStr":"{\"title\":\"ccfDNA analysis for the classification of adrenocortical adenomas.\",\"authors\":\"Mengjie Xu, David S Tourigny, Juliane Lippert, Ana Crastin, Silke Appenzeller, Miriam Asia, Oskar Podstawka, Gabrielle Smith, Yasir S Elhassan, Kassiani Skordilis, Alessandro Prete, Cristina L Ronchi\",\"doi\":\"10.1007/s40618-025-02540-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Somatic alterations are commonly observed in adrenocortical adenomas including cortisol-producing (CPA) [overt Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS)], aldosterone-producing (APA), and non-functioning (NFAT) tumors. We tested whether somatic variants could be detected in circulating cell-free DNA (ccfDNA) from patients with adenomas and potentially contribute to management strategies.</p><p><strong>Materials and methods: </strong>We investigated 44 patients (17 CPA-MACS, 9 CPA-CS, 12 APA, and 6 NFAT). 23 healthy subjects (HS) served as controls. ccfDNA was extracted from blood samples and quantified with fluorimeter. Tumor DNA (T-DNA) was isolated from paraffin embedded tissue in 17/44 cases. Matched ccfDNA/T-DNA were sequenced using a customized panel including 32 genes. Leucocyte DNA was used to filter out germline variants.</p><p><strong>Results: </strong>Patients with adenomas had higher total ccfDNA concentrations than HS [median 0.12 (IQR 0.05-0.19) vs. 0.05 (0.00-0.08) ng/µl, P < 0.001], with CPA-CS showing the highest ccfDNA levels [0.18 (0.05-0.47) ng/µl]. Within T-DNA, somatic variants were identified in 53% of adenomas: PRKACA in 2/7 CPA-CS, CTNNB1 in 3/5 CPA-MACS and 1/7 CPA-CS, KCNJ5 in 2/5 APA and CACNA1D in 1/5 APA. Somatic mutations were not detected in any of the investigated ccfDNA samples.</p><p><strong>Conclusions: </strong>Total ccfDNA concentrations are higher in patients with CPA-CS. Despite the presence of somatic variants in half of tumor samples, we did not detect any at ccfDNA level. Therefore, this approach appears ineffective for pre-operative detection of genetic alterations.</p>\",\"PeriodicalId\":48802,\"journal\":{\"name\":\"Journal of Endocrinological Investigation\",\"volume\":\" \",\"pages\":\"1207-1216\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049379/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Endocrinological Investigation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40618-025-02540-5\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/1 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Endocrinological Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40618-025-02540-5","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/1 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
ccfDNA analysis for the classification of adrenocortical adenomas.
Background: Somatic alterations are commonly observed in adrenocortical adenomas including cortisol-producing (CPA) [overt Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS)], aldosterone-producing (APA), and non-functioning (NFAT) tumors. We tested whether somatic variants could be detected in circulating cell-free DNA (ccfDNA) from patients with adenomas and potentially contribute to management strategies.
Materials and methods: We investigated 44 patients (17 CPA-MACS, 9 CPA-CS, 12 APA, and 6 NFAT). 23 healthy subjects (HS) served as controls. ccfDNA was extracted from blood samples and quantified with fluorimeter. Tumor DNA (T-DNA) was isolated from paraffin embedded tissue in 17/44 cases. Matched ccfDNA/T-DNA were sequenced using a customized panel including 32 genes. Leucocyte DNA was used to filter out germline variants.
Results: Patients with adenomas had higher total ccfDNA concentrations than HS [median 0.12 (IQR 0.05-0.19) vs. 0.05 (0.00-0.08) ng/µl, P < 0.001], with CPA-CS showing the highest ccfDNA levels [0.18 (0.05-0.47) ng/µl]. Within T-DNA, somatic variants were identified in 53% of adenomas: PRKACA in 2/7 CPA-CS, CTNNB1 in 3/5 CPA-MACS and 1/7 CPA-CS, KCNJ5 in 2/5 APA and CACNA1D in 1/5 APA. Somatic mutations were not detected in any of the investigated ccfDNA samples.
Conclusions: Total ccfDNA concentrations are higher in patients with CPA-CS. Despite the presence of somatic variants in half of tumor samples, we did not detect any at ccfDNA level. Therefore, this approach appears ineffective for pre-operative detection of genetic alterations.
期刊介绍：
The Journal of Endocrinological Investigation is a well-established, e-only endocrine journal founded 36 years ago in 1978. It is the official journal of the Italian Society of Endocrinology (SIE), established in 1964. Other Italian societies in the endocrinology and metabolism field are affiliated to the journal: Italian Society of Andrology and Sexual Medicine, Italian Society of Obesity, Italian Society of Pediatric Endocrinology and Diabetology, Clinical Endocrinologists’ Association, Thyroid Association, Endocrine Surgical Units Association, Italian Society of Pharmacology.
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