Genomic stratification and liquid biopsy in a rare adrenocortical carcinoma (ACC) case, with dual lung metastases
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PROVIDER: EGAC00001001138 | EGA |
REPOSITORIES: EGA
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Project description:Adrenocortical carcinoma is a rare malignancy with a poor prognosis and few treatment options. Molecular characterization of this cancer remains limited. We present a case of an adrenocortical carcinoma (ACC) in a 37-yr-old female, with dual lung metastases identified 1 yr following commencement of adjuvant mitotane therapy. As standard therapeutic regimens are often unsuccessful in ACC, we undertook a comprehensive genomic study into this case to identify treatment options and monitor disease progress. We performed targeted and whole-genome sequencing of germline, primary tumor, and both metastatic tumors from this patient and monitored recurrence over 2 years using liquid biopsy for ctDNA and steroid hormone measurements. Sequencing revealed the primary and metastatic tumors were hyperhaploid, with extensive loss of heterozygosity but few structural rearrangements. Loss-of-function mutations were identified in MSH2, TP53, RB1, and PTEN, resulting in tumors with mismatch repair signatures and microsatellite instability. At the cellular level, tumors were populated by mitochondria-rich oncocytes. Longitudinal ctDNA mutation and hormone profiles were unable to detect micrometastatic disease, consistent with clinical indicators of disease remission. The molecular signatures in our ACC case suggested immunotherapy in the event of disease progression; however, the patient remains free of cancer. The extensive molecular analysis presented here could be applied to other rare and/or poorly stratified cancers to identify novel or repurpose existing therapeutic options, thereby broadly improving diagnoses, treatments, and prognoses.
| S-EPMC6549567 | biostudies-literature
Project description:Adrenocortical carcinoma is a rare malignancy with a poor prognosis and few treatment options. Molecular characterization of this cancer remains limited. We present a case of an adrenocortical carcinoma (ACC) in a 37-yr-old female, with dual lung metastases identified 1 yr following commencement of adjuvant mitotane therapy. As standard therapeutic regimens are often unsuccessful in ACC, we undertook a comprehensive genomic study into this case to identify treatment options and monitor disease progress. We performed targeted and whole-genome sequencing of germline, primary tumor, and both metastatic tumors from this patient and monitored recurrence over 2 yr using liquid biopsy for ctDNA and steroid hormone measurements. Sequencing revealed the primary and metastatic tumors were hyperhaploid, with extensive loss of heterozygosity but few structural rearrangements. Loss-of-function mutations were identified in MSH2, TP53, RB1, and PTEN, resulting in tumors with mismatch repair signatures and microsatellite instability. At the cellular level, tumors were populated by mitochondria-rich oncocytes. Longitudinal ctDNA mutation and hormone profiles were unable to detect micrometastatic disease, consistent with clinical indicators of disease remission. The molecular signatures in our ACC case suggested immunotherapy in the event of disease progression; however, the patient remains free of cancer. The extensive molecular analysis presented here could be applied to other rare and/or poorly stratified cancers, to identify novel or repurpose existing therapeutic options, thereby broadly improving diagnoses, treatments, and prognoses.
| EGAS00001003497 | EGA
Project description:The occurrence of small intestinal metastases from primary lung cancer is rare. This report documents the case of a 57-year-old male patient initially diagnosed with non-metastatic lung adenocarcinoma, who presented with abdominal pain 6 months later. Postoperative pathological analysis confirmed the final diagnosis to be small intestinal metastasis from primary lung cancer. Thoracoscopic surgery and systemic chemotherapy were the preferred treatment options. However, the lung tumor spread to the small intestine, causing intestinal obstruction. As the patient could not tolerate anti-tumor therapy, only symptomatic treatment was provided. The patient experienced massive gastrointestinal bleeding and died the next day. Although small intestinal metastasis from lung cancer is rare and difficult to diagnose accurately, it should be considered when encountering a patient with lung cancer exhibiting abdominal symptoms and associated imaging findings. At this point, a pathological diagnosis should be performed immediately to determine the nature and source of the tumor. Furthermore, individualized treatment should be conducted in strict accordance with oncology guidelines. Of note, early detection and treatment are critical to ensure favorable outcomes.
| S-EPMC10161349 | biostudies-literature
Project description:Lung cancer is one of the most common and lethal cancers worldwide. Numerous medications targeting specific molecular alterations in non-small cell lung cancer have been introduced in the last decade and have revolutionized the clinical management of the disease. Their use has brought to a parallel evolution of molecular testing techniques to identify alterations in druggable molecular targets within the genetic material of the tumors. To perform molecular testing, biopsy or surgery tissue specimens are needed, which in addition allow the histological characterization of the tumors. Unfortunately, in real-life practice not all the patients are suitable for biopsy or surgery procedures. The use of liquid biopsy for blood extracted tumoral DNA analysis is a promising approach in unbiopsied cases, but it is also weighted by several methodological and technical limitations. We report here a case of histologically undiagnosed lung cancer managed with a liquid biopsy and subsequently with anti-EGFR treatment. Our report highlights that the use of liquid biopsy molecular testing in specific clinical situations can offer treatment opportunities for fragile patients affected by lung cancer.
| S-EPMC9694216 | biostudies-literature
Project description:IntroductionAdrenal tumors (ATs) encompass a wide differential diagnosis, necessitating a multi-step process for accurate identification. Liquid biopsy emerges as a promising non-invasive technique for distinguishing between malignant and benign, as well as hyperfunctioning and non-functioning cases. Recent studies have highlighted the potential of microRNAs as circulating biomarkers; however, their clinical utility remains underexplored. This study aims to validate the diagnostic performance of selected circulating microRNAs, (miR-483-5p, miR-210, miR-335 and miR-22-3p), identified through microRNA profiling studies, as markers of malignancy or cortisol hypersecretion in a cohort of patients with ATs.MethodsWe collected serum samples from 75 patients with ATs, including 50 cases of adrenocortical adenomas (ACA) and 25 cases of adrenocortical carcinomas (ACC), along with 15 controls. In the ACC subgroup, 16 samples were obtained preoperatively or upon detection of recurrence (active ACC group), while the remaining from disease-free patients with long-term follow-up. Among the 56 patients with ATs evaluated preoperatively (50 with ACAs and 6 with ACC), 26 had non-functioning tumors, 22 exhibited mild autonomous cortisol secretion, and 8 had Cushing syndrome. Quantitative real-time polymerase chain reaction was employed to analyze microRNA expression.ResultsCirculating levels of miR-483-5p and miR-210 were significantly elevated in patients with active ACC compared to both ACAs (p<0.001 and p=0.004, respectively) and controls (p=0.02 and p = 0.03, respectively). Notably, miR-483-5p serum levels were higher in patients with active ACC compared to disease-free ACC patients (p = 0.01). MiR-483-5p demonstrated the best diagnostic accuracy for distinguishing active ACC cases from ACAs, achieving a sensitivity of 81.3% and a specificity of 88%, and from disease-free ACC patients, reaching sensitivity of 81.3% and specificity of 89%. MiR-22-3p serum levels successfully differentiated patients with Cushing syndrome from those with non-functioning ATs (area under the curve=AUC=0.800, 95% CI: 0.653-0.953, p=0.01) and controls (AUC= 0.800, 95% CI: 0.610-0.990, p=0.02). Additionally, circulating miR-22-3p levels exhibited a significant correlation with traditional diagnostic tests for hypercortisolism.ConclusionThis study supports the potential of a liquid biopsy approach as an innovative method for diagnosing and monitoring patients with ATs, offering a complementary tool to existing diagnostic methods.
| S-EPMC11821491 | biostudies-literature
Project description:The optimal treatment paradigm for patients with oligometastatic non-small cell lung cancer (NSCLC) remains unclear. Some patients with oligometastatic disease experience prolonged remission after locally consolidative radiation therapy (RT), while others harbor micrometastatic disease (below limits of detection by imaging) and benefit from systemic therapy. To risk-stratify and identify the patients most likely to benefit from locally consolidative RT, we performed a multi-institutional cohort study of 1487 patients with oligometastatic NSCLC undergoing liquid biopsy analysis of circulating tumor DNA (ctDNA). In total, 1880 liquid biopsies were performed and approximately 20% of patients (n = 309) had ctDNA measured prior to RT and after their diagnosis of oligometastatic disease. Patients with undetectable ctDNA (pathogenic or likely pathogenic variants in plasma using the Tempus xF assay) before RT had significantly improved progression-free survival (PFS) (P = 0.004) and overall survival (OS) (P = 0.030). ctDNA maximum variant allele frequency (VAF) pre-RT and ctDNA mutational burden pre-RT were both significantly inversely correlated with PFS (maximum VAF P = 0.008, mutational burden P = 0.003) and OS (maximum VAF P = 0.007, mutational burden P = 0.045). These findings were corroborated by multivariate Cox proportional hazards models that included eight additional clinical and genomic parameters. Overall, these data suggest that in patients with oligometastatic NSCLC, pre-RT ctDNA can potentially identify the patients most likely to benefit from locally consolidative RT and experience prolonged PFS and OS. Similarly, ctDNA may be useful to identify undiagnosed micrometastatic disease where it may be appropriate to prioritize systemic therapies.
| S-EPMC10545784 | biostudies-literature
Project description:The optimal treatment for patients with oligometastatic non-small cell lung cancer (NSCLC) remains unclear. Some patients with oligometastatic disease can experience prolonged remission after locally consolidative radiation therapy (RT), while others harbor micrometastatic disease (below current limits of detection by imaging) that may benefit from further prioritization of systemic therapy. To better risk-stratify this population and identify the patients most likely to benefit from locally consolidative radiation therapy, we performed a multi-institutional cohort study of patients with oligometastatic NSCLC undergoing liquid biopsy analysis of circulating tumor DNA (ctDNA). Among this real-world cohort of 1,487 patients undergoing analysis (using the Tempus xF assay), a total of 1,880 ctDNA liquid biopsies along with paired clinical data were obtained across various timepoints. Approximately 20% (n=309) of patients had ctDNA obtained prior to RT and after their diagnosis of oligometastatic disease. Samples were de-identified and analyzed for mutational burden and variant frequencies of detectable deleterious (or likely deleterious) mutations in plasma. Patients with undetectable ctDNA before RT had significantly improved progression-free survival and overall survival compared to patients with detectable ctDNA prior to RT. In patients that received RT, 598 pathogenic (or likely deleterious) variants were identified. ctDNA mutational burden pre-RT and ctDNA maximum variant allele frequency (VAF) pre-RT were both significantly inversely correlated with both progression-free (P = 0.0031 for mutational burden, P = 0.0084 for maximum VAF) and overall survival (P = 0.045 for mutational burden, P = 0.0073 for maximum VAF). Patients without detectable ctDNA prior to RT had significantly improved progression-free survival (P = 0.004) and overall survival (P = 0.03) compared to patients with detectable ctDNA prior to RT. These data suggest that in patients with oligometastatic NSCLC, pre-radiotherapy ctDNA analysis can potentially identify the patients most likely to benefit from locally consolidative RT and experience prolonged progression-free and overall survival. Similarly, ctDNA may be useful to identify those patients with undiagnosed micrometastatic disease, in whom it may be appropriate to prioritize systemic therapy.
| S-EPMC10055612 | biostudies-literature
Project description:ContextAdrenocortical carcinoma (ACC) is a rare endocrine malignancy that affects patients across the age spectrum. Although the overall survival in patients with ACC is poor, there is significant heterogeneity in terms of outcomes, presentation, and underlying genetic drivers.Evidence acquisitionThis review is based on the evidence collected from primary research studies, expert reviews, and published guidelines. The studies were identified through PubMed search with key words "adrenocortical carcinoma," "prognosis," "pathology," and "genetics." The PubMed search was complemented by authors' expertise, research, and clinical experience in the field of ACC.Evidence synthesisIdentification of biomarkers has been critical to gain better insight into tumor behavior and to guide therapeutic approach to patients. Tumor stage, resection status, and Ki67 are pathological tumor characteristics that have been identified as prognosticators in patients with ACC. Cortisol excess also correlates with worse prognosis. Clinical and histopathological characteristics help stratify patient outcomes, yet still up to 25% of patients have a different outcome than predicted. To bridge this gap, comprehensive genomic profiling studies have characterized additional profiles that correlate with clinical outcomes. In addition, studies of clinically applicable molecular markers are under way to further stratify outcomes in patients with ACC tumors.ConclusionsClinical predictors in combination with pathological markers play a critical role in the approach to patients with ACC. Recent advances in genetic prognosticators will help extend the stratification of these tumors and contribute to a personalized therapeutic approach to patients with ACC.
| S-EPMC8947319 | biostudies-literature
Project description:Metastasis to the left atrium is exceptionally uncommon, occurring at a rate of only 3.1%. The clinical manifestations of lung cancer metastasizing to the heart can vary widely. They range from paraneoplastic syndrome, dyspnea, and ST-segment elevation on an electrocardiogram to no clinically significant symptoms. Diverging from typical metastatic patterns observed in lung cancer, this case report presents a detailed description, from the perspective of the microenvironment, of a rare instance where lung cancer metastasized to the mediastinal lymph nodes, adrenal glands, brain, and notably, the left atrium, in a non-smoking female patient.
| S-EPMC11424542 | biostudies-literature
Project description:The iCAP is a tool for blood-based diagnostics that addresses the low signal-to-noise ratio of blood biomarkers by using cells as biosensors. The assay exposes patient serum to standardized cells in culture and classifies disease by AI analysis of gene expression readouts from the cells. This method simplifies the complexity of blood into a concise readout in a scalable cell-based assay. We developed the LC-iCAP as a rule-out test for nodule management in CT-based lung cancer screening. The assay achieved an AUC of 0.63 (95% CI 0.50-0.75) in blind temporal validation with retrospective samples. When integrated with CT data after validation, it demonstrated 90% sensitivity, 67% specificity and 95% NPV using an estimated 25% prevalence, significantly outperforming the Mayo Clinic model and potentially reducing unnecessary follow-up procedures. Analytical validation demonstrated LC-iCAP reproducibility, identified unwanted variation from long-term sample storage and indicated enrichment of hypoxia signaling in the differential assay readout.
2025-08-07 | GSE275699 | GEO