JCO precision oncology最新文献

{"title":"Clinical Relevance of Post-Treatment Circulating Tumor DNA Detection in Early Breast Cancer Using a Tissue-Free Epigenomic Assay: A 2-Year Landmark Analysis.","authors":"Thomas W P Friedl, Peter A Fasching, Andreas D Hartkopf, Hans Tesch, Ralf Lorenz, Georg Heinrich, Jens-Uwe Blohmer, Tanja Fehm, Volkmar Mueller, Andreas Schneeweiss, Matthias W Beckmann, Matthias Ruebner, Nadia Harbeck, Klaus Pantel, Derek Dustin, Mingyang Cai, Brigitte Rack, Wolfgang Janni","doi":"10.1200/PO-26-00095","DOIUrl":"https://doi.org/10.1200/PO-26-00095","url":null,"abstract":"<p><strong>Purpose: </strong>Circulating tumor DNA (ctDNA) may serve as a biomarker to facilitate early identification of asymptomatic distant tumor spread in patients with breast cancer. The primary objective of this study was to assess clinical validity and prognostic value of post-treatment tissue-free ctDNA detection by evaluating its sensitivity for distant metastatic recurrence and its association with long-term outcomes.</p><p><strong>Patients and methods: </strong>Plasma samples were prospectively collected from patients with stage I-III early breast cancer who participated in the adjuvant SUCCESS-A phase III clinical trial (ClinicalTrials.gov identifier: NCT02181101). In this study, plasma samples collected approximately 2 years after completion of adjuvant chemotherapy from 313 SUCCESS A patients without evidence of prior disease recurrence were retrospectively analyzed using a tissue-free epigenomic ctDNA assay (Guardant Reveal). Survival analyses were performed using a landmark approach based on the time of sample collection.</p><p><strong>Results: </strong>Overall, ctDNA was detected in 18 of 313 samples (5.8%). Of all ctDNA detected samples, 94% (17/18) were from patients who subsequently developed a distant recurrence, with ctDNA detected at a median interval of 7.9 months before recurrence. ctDNA positivity was strongly associated with a significantly shorter distant recurrence-free interval (hazard ratio [HR], 33.3 [95% CI, 4.12 to 268]; <i>P</i> < .0001) and poorer overall survival (HR, 27.3 [95% CI, 1.15 to 647]; <i>P</i> < .0001). The sensitivity for distant recurrence in patients who had a sample collected within 1 year before recurrence was 73% (11/15). The specificity in nonrecurred patients was 99.6% (267/268).</p><p><strong>Conclusion: </strong>Tissue-free detection of ctDNA 2 years after adjuvant chemotherapy was highly prognostic in an early-stage breast cancer cohort, and can be used to stratify patients with early-stage breast cancer at high risk for recurrence during follow-up who may benefit from early interventions.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600095"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Cell Lung Cancer Transformation in Actionable Genomic Alteration-Negative Non-Small Cell Lung Cancer With Response to Tarlatamab: A Case Report.","authors":"Cody E Cotner, Yin P Hung, Mari Mino-Kenudson, Justin F Gainor, Jessica J Lin","doi":"10.1200/PO-26-00538","DOIUrl":"https://doi.org/10.1200/PO-26-00538","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600538"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting Oral Cancer From Precursor Lesions: Assessing Current Methods and Future Directions.","authors":"Michael E Troka, James C Gates","doi":"10.1200/PO-26-00107","DOIUrl":"https://doi.org/10.1200/PO-26-00107","url":null,"abstract":"<p><strong>Purpose: </strong>Oral potentially malignant disorders (OPMDs) pose a significant clinical challenge due to their potential to develop into oral squamous cell carcinoma, a prevalence of 4%-5% of the US population, and malignant transformation rates that approach 10%. Current methods to assess risk of OPMD progression to oral cancer are fraught with limitations and incompletely predict risk.</p><p><strong>Methods: </strong>We review existing diagnostic and prognostic tools for OPMDs, examining their validation evidence, performance characteristics, and clinical utility.</p><p><strong>Results: </strong>Although some tools provide rule-in or rule-out capabilities, each tool interrogates a single biological layer, and none provides comparable positive predictive value and negative predictive value in a single tool.</p><p><strong>Conclusion: </strong>A framework integrating multiomic data across multiple different biologic processes and time points inclusive of benign mimics is needed to better identify which lesions are true OPMDs, and which warrant escalation and intervention versus surveillance or de-escalation.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600107"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Predictive Biomarkers for Chemoradiotherapy Response in Rectal Cancer.","authors":"Mee-Na Park, Junho Kang, Jeong-Woo Hwang, Hye Won Lee, Incheol Seo, Shin Kim, Sang Jun Byun, Woon Kyung Jeong, Seong Kyu Baek, Sung Uk Bae","doi":"10.1200/PO-26-00262","DOIUrl":"https://doi.org/10.1200/PO-26-00262","url":null,"abstract":"<p><strong>Purpose: </strong>Chemoradiotherapy (CRT) is a standard treatment for rectal cancer, yet patients show marked variability in response. Identifying reliable biomarkers that predict CRT response remains an unmet clinical need.</p><p><strong>Methods: </strong>Pretreatment biopsy samples from patients who received neoadjuvant CRT were analyzed using RNA sequencing. Differentially expressed genes (DEGs) were identified between responders and nonresponders, followed by functional enrichment analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. To complement DEG-based results, gene-set enrichment analysis (GSEA) was performed to assess pathway activity across the ranked transcriptome and to prioritize biologically relevant pathways. Pathway-derived gene signatures were evaluated using receiver operating characteristic curves and validated in three independent data sets.</p><p><strong>Results: </strong>A total of 1,477 DEGs were detected, including 729 upregulated and 748 downregulated genes in responders. Functional enrichment analysis indicated immune activation and epithelial polarity in responders, whereas nonresponders showed enrichment of extracellular matrix organization, focal adhesion, and phosphoinositide 3-kinase-protein kinase B signaling. GSEA further identified four pathways associated with CRT response: antigen presentation, extracellular matrix-receptor interaction, focal adhesion, and drug metabolism. Among these, the antigen presentation pathway consistently predicted treatment response across data sets. Elastic net regression defined a six-gene signature (<i>KLRC1</i>, <i>CTSS</i>, <i>HLA-DMA</i>, <i>HLA-DQB1</i>, <i>HLA-DQB2</i>, and <i>CIITA</i>) with strong predictive performance, with area under the curve values ranging from 0.76 to 0.81.</p><p><strong>Conclusion: </strong>These genes participate in major histocompatibility complex class II antigen-processing and immune-regulatory pathways that enhance CD4 T-cell activation. Overall, the findings indicate that an immune-active, antigen presentation phenotype underlies radiosensitivity in rectal cancer and that the six-gene signature may serve as a biomarker to guide personalized treatment strategies.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600262"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Disease-Agnostic Genomic Liquid Biopsy in Complex Diagnoses: Real-Life Example of cfChIP-Seq in a Fever of Unknown Origin.","authors":"Orly Agmon Gutin, Jenia Gutin, Dania Jaber, Gabriella Snoyman, Bara Hmeidat, Ronen Sadeh, Benjamin Glaser, Nir Friedman","doi":"10.1200/PO-25-01235","DOIUrl":"10.1200/PO-25-01235","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2501235"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13465709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Potential Clinical Actionability of Genomic Alterations in Early-Onset Versus Later-Onset GI Cancers.","authors":"Lawrence W Wu, Jimyung Park, Sungjoo Jang, Ryan H Moy","doi":"10.1200/PO-26-00389","DOIUrl":"https://doi.org/10.1200/PO-26-00389","url":null,"abstract":"<p><strong>Purpose: </strong>As biomarker-directed therapy increasingly shapes GI oncology, it remains unclear whether early-onset (EO) and later-onset (LO) GI cancers harbor comparable opportunities for clinically actionable targeting. We compared the landscape of potentially actionable genomic alterations in EO versus LO GI cancers using American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange v19.0.</p><p><strong>Methods: </strong>GI tumor samples were assigned to 10 prespecified tumor groups using OncoTree codes. Samples were annotated with OncoKB therapeutic levels and classified as potentially actionable if they harbored at least one level 1-3B alteration. EO and LO disease were defined as age at sequencing <50 years and ≥50 years, respectively. Group-wise comparisons used Wilcoxon rank-sum, chi-square, or Fisher exact testing as appropriate and with false discovery rate correction. Multivariable logistic regression evaluated age group associations overall and within tumor groups.</p><p><strong>Results: </strong>Among 53,945 GI tumor samples, 10,573 (19.6%) were EO and 43,372 (80.4%) were LO. EO tumors had lower prevalence of potentially actionable alterations in colorectal (71% <i>v</i> 78.1%, q < 0.001), esophagogastric (53.3% <i>v</i> 57.9%, q = 0.0097), GI stromal tumor (GIST) (75.1% <i>v</i> 90.9%, q < 0.001), liver (25.4% <i>v</i> 35.4%, q = 0.0021), and pancreatic tumors (82.9% <i>v</i> 90.7%, q < 0.001). In the overall model, LO status was associated with higher odds of potential actionability (odds ratio, 1.39 [95% CI, 1.33 to 1.47]; <i>P</i> < .001). Tumor group-specific associations persisted in colorectal, GIST, liver, and pancreatic tumors after multivariable adjustment.</p><p><strong>Conclusion: </strong>Potential clinical actionability differs between EO and LO GI cancers in a tumor lineage-specific manner. Several major EO GI tumor groups appear relatively depleted of potentially actionable alterations, suggesting that the expanding therapeutic reach of precision oncology may not be distributed evenly across age-defined GI cancer populations and underscoring the need for EO-focused biomarker discovery and therapeutic development.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600389"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APUC-6 Genes as a Potential Prognostic and Predictive Biomarker in the CHAARTED Prostate Cancer Trial.","authors":"Xiaolei Shi, Amol C Shetty, Jarey Wang, Yang Song, Philip A Sutera, Matthew P Deek, Krishnan R Patel, Ravi A Madan, Chad Tang, James Proudfoot, Elai Davicioni, Arif Hussain, Paul Nguyen, Christopher Sweeney, Ella Boytim, Kristine P Lacuna, Charles J Ryan, Emmanuel S Antonarakis, Phuoc T Tran, Justin Hwang","doi":"10.1200/PO-25-01012","DOIUrl":"10.1200/PO-25-01012","url":null,"abstract":"<p><strong>Purpose: </strong>A six-gene panel involved in androgen production, uptake, and conversion (APUC-6: <i>HSD3B1</i>, <i>HSD3B2</i>, <i>CYP3A43</i>, <i>CYP11A1</i>, <i>CYP11B1</i>, <i>CYP17A1</i>) may define distinct clinical outcomes in metastatic prostate cancer. This study evaluated the prognostic and predictive value of APUC-6 expression in metastatic castration-sensitive prostate cancer (mCSPC).</p><p><strong>Methods: </strong>Transcriptomic data from 160 patients in the phase III Eastern Cooperative Oncology Group-ACRIN E3805 CHAARTED trial were analyzed. Patients were stratified into four subgroups based on APUC-6 and androgen receptor (<i>AR</i>) gene expression. Clinical outcomes including time to clinical progression (ttCP), time to castration resistance (ttCR), and overall survival (OS) were assessed within the androgen deprivation therapy (ADT) and docetaxel plus ADT (D-ADT) arms. Interaction testing evaluated the predictive value of APUC-6/<i>AR</i> status. Subgroup analyses were also performed by Decipher genomic risk.</p><p><strong>Results: </strong>Patients with APUC-6-high/AR-low expression showed significantly improved ttCP (hazard ratio [HR], 0.43 [95% CI, 0.22 to 0.82]; <i>P</i> = .0092), ttCR (HR, 0.56 [95% CI, 0.32 to 1]; <i>P</i> = .049), and OS (HR, 0.31 [95% CI, 0.16 to 0.61]; <i>P</i> = .0003), but did not appear to benefit from the addition of docetaxel. Conversely, APUC-6-low/<i>AR</i>-low patients demonstrated significantly improved outcomes with D-ADT (ttCP: HR, 0.37 [95% CI, 0.21 to 0.65]; <i>P</i> = .00036; ttCR: HR, 0.38 [95% CI, 0.23 to 0.64]; <i>P</i> = .00017; OS: HR, 0.39 [95% CI, 0.21 to 0.72]; <i>P</i> = .0019). Statistical interaction analysis supported that patients with APUC-6-low/<i>AR</i>-low expression were more likely to benefit from docetaxel (HR, 0.36 [95% CI, 0.19 to 0.66]; <i>P</i> = .001). For patients with a high Decipher genomic classifier score, those in the APUC-6-low subgroup had improved survival with D-ADT, whereas those in the APUC-6-high subgroup did not gain any additional benefit from docetaxel.</p><p><strong>Conclusion: </strong>APUC-6 expression and <i>AR</i> gene expression define clinically relevant subgroups in mCSPC and may enhance precision medicine treatment approaches in combination with other transcriptomic biomarkers.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2501012"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk-Reducing Interventions in Women With Pathogenic Variants in Breast Cancer Susceptibility Genes.","authors":"Emily M Russell, Sarah M Nielsen, Rachel E Ellsworth, Heidi Chwan Ko, Rebecca A Previs, Daniel E Pineda-Alvarez, Edward D Esplin, Kevin Hughes, Stacy W Gray, Nadine M Tung, Allison W Kurian","doi":"10.1200/PO-26-00373","DOIUrl":"10.1200/PO-26-00373","url":null,"abstract":"<p><strong>Purpose: </strong>Recommendations for clinical management of women with germline pathogenic variants (PVs) in breast cancer susceptibility genes vary by gene. The goal of this study was to examine the utilization of risk-reducing strategies and treatments in women with germline PVs in breast cancer susceptibility genes.</p><p><strong>Methods: </strong>This cross-sectional study identified women with a PV in at least one of 13 breast cancer susceptibility genes from germline panel testing at a single commercial laboratory between 2015 and 2023. Paired health care claims data for 12 months after genetic testing were evaluated to estimate the utilization of risk-reducing mastectomy and salpingo-oophorectomy, breast magnetic resonance imaging (MRI), and pancreatic screening (magnetic resonance cholangiopancreatography or endoscopic ultrasound) in these women. Multivariable logistic regression models were used to evaluate the association of clinicodemographic factors and genetic testing results with intervention utilization.</p><p><strong>Results: </strong>Of 3,959 women with a PV (2,088 cancer-free; 1,871 with primary breast cancer diagnosed ≤120 days before genetic testing), the average age at testing was 45 years, 67% were White, and 90% reported a family history of cancer. Breast MRI was used by 33% of cancer-free women and 31% of women with breast cancer after genetic testing; pancreatic screening occurred in <11% of the eligible population. Women with PVs in <i>BRCA1</i>/<i>2</i> versus other breast cancer susceptibility genes had higher odds of risk-reducing mastectomy (cancer-free: odds ratio 7.2 [95% CI, 3.5 to 14.5]; with cancer: 6.0 [95% CI, 4.2 to 8.5]) and salpingo-oophorectomy (cancer-free: 7.2 (95% CI, 4.6 to 11.3]; with cancer: 13.8 [95% CI, 9.7 to 19.7]).</p><p><strong>Conclusion: </strong>Utilization of risk-reducing surgery was highest in women with <i>BRCA1</i>/<i>2</i> PV. Pancreatic screening was low in all patients. Future studies are needed to examine the factors underlying these trends.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600373"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast Neuroendocrine Carcinoma: Molecular Insights Beyond Histology.","authors":"Christopher J Schwartz, Tanner Mack, William Travis, Hong Zhang, Nour Abuhadra, Risa Kiernan, Giacomo Montagna, Edi Brogi, Fresia Pareja, Hannah Y Wen, Dara S Ross","doi":"10.1200/PO-26-00416","DOIUrl":"10.1200/PO-26-00416","url":null,"abstract":"<p><strong>Purpose: </strong>Primary breast neuroendocrine carcinomas (NECs) are rare, high-grade malignancies that are frequently grouped with invasive breast carcinomas with neuroendocrine differentiation (IBC-NED), despite uncertain biological equivalence. We sought to define the clinicopathologic, immunophenotypic, and genomic features of breast NEC and to determine whether they represent a biologically distinct entity.</p><p><strong>Methods: </strong>We performed a retrospective analysis of 24 primary breast NECs and compared them with 28 grade-matched IBC-NEDs. Clinicopathologic features, treatment response, and outcomes were evaluated. Immunohistochemical profiling included neuroendocrine and breast lineage markers and retinoblastoma (Rb) expression. Targeted tumor-normal next-generation sequencing was performed in a subset of NEC (n = 10) and IBC-NED (n = 7) to characterize genomic alterations and pathway-level differences.</p><p><strong>Results: </strong>Breast NECs were predominantly estrogen receptor (ER)-negative/human epidermal growth factor receptor-2-negative (63%) and frequently exhibited small cell morphology. Despite radiographic response to neoadjuvant chemotherapy, no patients achieved pathologic complete response. Immunophenotypically, NECs demonstrated diffuse neuroendocrine marker expression and frequent loss of Rb protein (93%), consistent with RB pathway disruption. Compared with IBC-NED, NECs showed significantly lower ER expression and reduced GATA3 positivity. Genomically, NECs were enriched for <i>TP53</i> alterations (90% <i>v</i> 33%, <i>P</i> < .05) and more frequently harbored <i>RB1</i> alterations (60% <i>v</i> 14%), with concurrent <i>TP53</i>/<i>RB1</i> alterations in 50% of cases. Alterations in the PI3K pathway were also observed in NECs. By contrast, IBC-NED demonstrated recurrent luminal-type copy-number alterations, including amplifications in <i>FGFR1</i> and <i>CCND1</i>.</p><p><strong>Conclusion: </strong>Breast NEC is characterized by a distinct clinicopathologic and molecular profile compared with grade-matched IBC-NED, defined by frequent <i>TP53</i> and <i>RB1</i> alterations, RB pathway disruption, and limited response to neoadjuvant therapy. These findings support classification of breast NEC as a biologically distinct subtype and highlight potential avenues for biomarker-driven therapeutic strategies in this rare malignancy.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600416"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13496037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Landscape of Early-Onset Colorectal Cancer: A Comparative Analysis With Average-Onset Metastatic Colorectal Cancer in a Real-World NGS Cohort.","authors":"Ji Eun Shin, Eunbyeol Lee, Sang Yun Ha, Sung Hee Lim, Yong Beom Cho, Young Suk Park, Jeeyun Lee, Seung Tae Kim","doi":"10.1200/PO-26-00184","DOIUrl":"10.1200/PO-26-00184","url":null,"abstract":"<p><strong>Purpose: </strong>The incidence of early-onset colorectal cancer (EOCRC), defined as colorectal cancer (CRC) diagnosed before age 50 years, has been rising globally, in contrast to declining rates in older populations. However, despite its distinct clinical features, the genomic characteristics of EOCRC and its biological relationship to average-onset CRC (AOCRC) remain incompletely defined, particularly in the metastatic setting.</p><p><strong>Methods: </strong>We conducted a genomic analysis of patients with metastatic CRC who underwent next-generation sequencing (NGS) as part of routine clinical practice. Using targeted NGS panels (TruSight Oncology 500 and Oncomine Comprehensive Assay), we analyzed the genomic landscape of 1,892 patients, including 376 with EOCRC and 1,516 with AOCRC. Genomic alteration frequencies were compared between age groups, and age-stratified analyses were performed to evaluate associations between patient age and recurrent genomic alterations.</p><p><strong>Results: </strong>The overall genomic landscape was largely similar between EOCRC and AOCRC, with comparable frequencies of canonical CRC drivers, including <i>TP53</i>, <i>APC</i>, and <i>KRAS</i>. <i>MYC</i> alterations were significantly more frequent in EOCRC than in AOCRC. By contrast, age-stratified analyses revealed an inverse association between age at diagnosis and alteration rates in specific DNA damage repair-related genes and tumor suppressor genes, including <i>BRCA2</i>, <i>BARD1</i>, <i>FAT1</i>, <i>HIST1H1C</i>, and <i>LRP1B</i>, whereas canonical drivers showed no significant age-dependent trends.</p><p><strong>Conclusion: </strong>In metastatic disease, EOCRC shares a conserved canonical genomic backbone with AOCRC, indicating that it is not a genomically distinct entity. Nevertheless, limited binary differences involving <i>MYC</i> and broader age-dependent enrichment of specific DNA damage response-related alterations suggest that CRC arising at younger age may reflect distinct age-associated biological vulnerabilities.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600184"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}