JCO precision oncology最新文献

{"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":"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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619329/pdf/","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":"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}

{"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":"Pemigatinib in the Treatment of Metastatic, Inflammatory Triple-Negative Breast Cancer With <i>FGFR2</i> Rearrangement: A Case Report and Review of the Literature.","authors":"Nihaal Reddy, Katarina Vasiljevic, Rebecca Shatsky","doi":"10.1200/PO-25-00628","DOIUrl":"10.1200/PO-25-00628","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2500628"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722239","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":"Multiomic Characterization of a Rare Case of Pediatric Acute Leukemia With a Novel <i>ANGPT1::HOXA10-AS</i> Fusion.","authors":"Haley Newman, Derek Wong, Jeffrey Schubert, Jinhua Wu, Juan Santana, Ariel Long, Zirui Zhou, Feng Xu, Jiani Chen, Moe Takeda, Lisa Eidenschink Brodersen, Kathrin M Bernt, Minjie Luo, Sarah K Tasian, Marilyn M Li, Yiming Zhong","doi":"10.1200/PO-26-00409","DOIUrl":"10.1200/PO-26-00409","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600409"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874103","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":"Beyond the <i>P</i> Value: A Systematic Framework for Interpreting Oncology Clinical Trials.","authors":"Ruyue Li, Xue Dong, Xiujing Yao, Wenjie Chen, Hao An, Yintao Li","doi":"10.1200/PO-26-00271","DOIUrl":"10.1200/PO-26-00271","url":null,"abstract":"<p><p>In oncology, interpreting clinical trials solely through statistical significance (<i>P</i> < .05) often conflates true biological futility with methodological false negatives. This binary oversimplification risks prematurely abandoning active therapies while wasting resources on futile programs. We aimed to develop a structured framework to evaluate late-phase trials beyond simple <i>P</i> value assessments. Through a critical review of literature and landmark late-phase oncology trials, we analyzed common failure mechanisms and methodological pitfalls to construct a comprehensive, three-step methodology for the post hoc evaluation of negative studies. The review yielded a synthesized framework that approaches trial interpretation through three sequential steps. First, classification stratifies trials into five distinct categories: true negatives, false negatives, inconclusive trials, positive but irrelevant results, and nonsuperior but clinically valuable. Second, diagnosis uses root-cause analysis to identify underlying trial design flaws, execution biases, or statistical pitfalls. Third, recommendations outline targeted actionable strategies, including trial redesign, supplementary biomarker validation, precision medicine approaches, or scientific confirmation of therapeutic futility. This framework shifts trial interpretation from a simple win/loss assessment to a nuanced, value-based strategy. By systematically dissecting the root causes of trial failures, it empowers researchers to rescue therapies with latent clinical benefit or confidently confirm futility, thereby optimizing the evidence landscape for precision oncology.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600271"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13496032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760529","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":"Molecular Response Assessment From Circulating Tumor DNA in Patients With Ovarian Cancer Treated With the WEE1 Inhibitor Azenosertib.","authors":"Jinkil Jeong, Jianhui Ma, Mona Abed, Heekyung Chung, Doris Kim, Nandini Molden, Divya Rajendran, Changhwan Shim, Danielle D Jandial, Fiona Simpkins, Funda Meric-Bernstam, Leslie M Randall, Mark R Lackner, Olivier Harismendy","doi":"10.1200/PO-25-00844","DOIUrl":"10.1200/PO-25-00844","url":null,"abstract":"<p><strong>Purpose: </strong>Molecular response (MR) based on circulating tumor DNA (ctDNA) is emerging as a promising early biomarker of treatment efficacy in solid tumors; however, its clinical utility in high-grade serous ovarian cancer (HGSOC) remains to be established. This study evaluates the potential predictive value of ctDNA-based MR in with patients HGSOC treated with the WEE1 inhibitor azenosertib.</p><p><strong>Methods: </strong>Plasma cell-free DNA was collected at baseline and after the first and/or second cycle of treatment from 123 patients with recurrent HGSOC enrolled in clinical trials of azenosertib (N = 123). Using the set samples evaluable by high throughput DNA sequencing, MR was defined as a reduction of <i>TP53</i> variant allelic fraction >50% at the earliest evaluable on-treatment time point. MR was compared with radiographic response per Response Evaluation Criteria in Solid Tumors v1.1, time to progression (TTP), and CA-125 dynamics.</p><p><strong>Results: </strong>Molecular responders showed a higher objective response rate (<i>P</i> = .012, odds ratio = 0.26), greater tumor shrinkage (<i>P</i> = 5.1e-5, Kruskal-Wallis), and a significantly longer TTP than nonresponders (TTP median 5.49 months <i>v</i> 2.69 months, <i>P</i> = 3.8e-5, hazard ratios [HR] = 0.43). MR was able to identify patients with prolonged survival among those having stable disease at the first radiographic assessment (<i>P</i> = 3.8e-3, HR = 0.44), and their MR preceded the best overall response by several weeks. Accounting for matching collection time points, MR was evaluable in more patients than CA-125, 88% (102 of 116) versus 71% (85 of 116), respectively, leading to similar predictive value (HR = 0.41 <i>v</i> 0.45, TTP evaluation).</p><p><strong>Conclusion: </strong>Our findings support the validity and potential clinical utility of ctDNA-based MR as a minimally invasive, rapid, and reliable early surrogate end point in HGSOC.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2500844"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828059","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":"Establishing a Multicenter Personalized Medicine Program in Childhood, Adolescent, and Young Adult Cancer in Spain: The SEHOP-PENCIL Project.","authors":"Andrea Vilaplana, Asbleidy Carolina Torres, Adela Escudero López, Elisa Izquierdo, Sergio Manresa-Vera, Josep Escrivá-Fernández, Piedad Alba-Pavón, Lide Alaña, Angela Gutierrez-Camino, Carlos Rodríguez-Antolín, Clara Venegas Mascaró, Sonia Paco Mercader, Noelia Salvador, Ana Chamorro-Vera, Teresa Imízcoz, Elena Panizo Morgado, Beatriz Vergara-Muñoz, Antonio Juan-Ribelles, Nuria Benavent, Alicia Castañeda Heredia, Carlota Rovira Zurriaga, Lorena Valero-Arrese, Raquel Díaz-Merchán, Irene Manzano-Benito, Saint T Cervera, Laura García-Calvo, Irene Jiménez, Nerea Domínguez-Pinilla, Cristina Nova-Lozano, Isabel Cuadrado-Torroglosa, Jesús Sánchez-Ruiz, Tamara Mondejar, Antonio Pérez-Martínez, Ana Fernández-Teijeiro, Palma Solano-Páez, Josep Roma, Jaime Font de Mora, Bárbara Meléndez, Alba Rubio-San-Simón, Cristina Saiz-Ladera, Itziar Astigarraga, Adela Cañete, Javier Alonso, Cinzia Lavarino, Ana Patiño-García, Lucas Moreno, Aroa Soriano","doi":"10.1200/PO-26-00074","DOIUrl":"10.1200/PO-26-00074","url":null,"abstract":"<p><p>Pediatric cancer care in Spain lacked a national personalized medicine program. The SEHOP-PENCIL initiative, established by the SEHOP, was designed to address this gap. A national survey identified the genomic sequencing needs of hospitals treating pediatric patients with cancer. Results showed improved access to targeted next-generation sequencing panels but revealed persistent variability in implementation, limited availability of advanced sequencing (whole-exome sequencing, whole-genome sequencing, RNA sequencing, and DNA methylation profiling), and gaps in cancer predisposition clinics and molecular tumor boards (MTBs). SEHOP-PENCIL is organized as a network of 10 specialized genomic centers serving 45 hospitals through a centralized inclusion system. The program standardizes patient eligibility, genomic workflows, and result interpretation, supported by a national MTB. This framework enables informed clinical decision making, ensures access to molecular diagnosis and innovative therapies, and supports systematic data collection to advance pediatric cancer research and personalized care. SEHOP-PENCIL represents a pioneering national model for integrating precision oncology into pediatric cancer care in Spain. By fostering collaboration, standardizing genomic practices, and promoting equitable access, it aims to reduce disparities and improve outcomes, offering a scalable example for other decentralized health care systems.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600074"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874058","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":"Age-Specific Ovarian Cancer Risk Among Individuals With Pathogenic Variants in <i>PALB2</i>.","authors":"Koki Takabatake, Nicolas Kubista, Maria Sol Rosito, Yue Zhang, Stephen B Gruber, Gregory Idos, Giovanni Parmigiani, Danielle Braun","doi":"10.1200/PO-26-00167","DOIUrl":"https://doi.org/10.1200/PO-26-00167","url":null,"abstract":"<p><strong>Purpose: </strong>Pathogenic germline variants (PGVs) in <i>PALB2</i> are well-established risk factors for breast cancer, but their association with ovarian cancer (OC) remains less characterized. This study estimates age-specific OC risk among <i>PALB2</i> PGV carriers using a Bayesian segregation analysis approach.</p><p><strong>Methods: </strong>Family history, including OC diagnoses, was collected from probands with PGVs in <i>PALB2</i> from the Clinical Cancer Genomics Cancer Research Network (CCGCRN). CCGCRN is a consortium of 31 active community-based oncogenetic practices across 50 states in the United States and four countries in Latin America. A total of 140 probands with PGVs in <i>PALB2</i> were identified in CCGCRN, and family history was reported on 5,188 relatives (average family size is 38 individuals). Overall, 30 women had OC; of these, 5 cases were among probands and the remaining were among reported relatives. Age-specific penetrance of OC was estimated using the <i>penetrance</i> R package that employs a parametric Bayesian segregation analysis estimation approach, leveraging the family history.</p><p><strong>Results: </strong>The cumulative lifetime risk for OC for female carriers of <i>PALB2</i> PGVs at age 80 years was estimated to be 5.38% (95% CI [2.94 to 8.26]). This is significantly greater than the general population risk of 1.10% from the SEER data.</p><p><strong>Conclusion: </strong>We estimated a significantly increased risk of OC among individuals with <i>PALB2</i> PGVs compared with the SEER general population. However, our estimated credible interval was wide, likely because of the small sample number of probands and small number of OC cases. Further studies should continue to explore the association between PGVs in <i>PALB2</i> and OC risk.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600167"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828879","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}