JCO precision oncology最新文献

{"title":"Erratum: Tumor Characteristics Associated With Preoperatively Detectable Tumor-Informed Circulating Tumor DNA in Patients With Renal Masses Suspicious for Renal Cell Carcinoma.","authors":"","doi":"10.1200/PO-24-00733","DOIUrl":"https://doi.org/10.1200/PO-24-00733","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400733"},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582370","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":"Updated Survival Follow-Up for Phase Ib Trial of the Histone Deacetylase Inhibitor Abexinostat With Pazopanib in Patients With Solid Tumor Malignancies.","authors":"Erica S Tsang, Rahul R Aggarwal, Emily K Bergsland, Susan Calabrese, Alexandrine Rozie, Sibapriya Chaudhuri, Mallika S Dhawan, Nela Pawlowska, Jennifer Grabowsky, Scott Thomas, Pamela N Munster","doi":"10.1200/PO.24.00328","DOIUrl":"https://doi.org/10.1200/PO.24.00328","url":null,"abstract":"<p><strong>Purpose: </strong>Histone deacetylase (HDAC) inhibition downregulates hypoxia-inducible factor-1α and modulates multiple metabolomic pathways relevant in cancer. Here we report a potential novel biomarker to predict exceptional responders (>3 years) in patients receiving HDAC and vascular endothelial growth factor (VEGF) inhibition.</p><p><strong>Patients and methods: </strong>Patients with solid tumor malignancies were enrolled in this phase Ib trial of abexinostat (4/7 ×21 days) and pazopanib (28/28 days), with a dose expansion in renal cell carcinoma (RCC). Plasma was analyzed for metabolomics and peripheral blood mononuclear cells (PBMCs) for VEGF and HDAC2 expression levels.</p><p><strong>Results: </strong>Fifty-one patients were enrolled: n = 36 patients in dose escalation and n = 15 in dose expansion. After the initial report in 2017, six patients had remained on study: four with RCC and one each with medullary thyroid and thymic neuroendocrine carcinoma. One patient with RCC remains on treatment for >11 years after progression on five systemic therapies. Overall, the median duration of therapy measured 5.6 (1-133) months. The median duration of therapy in exceptional responders measured 44.1 (39.8-133+) months. The median overall survival in patients with high PBMC HDAC2 expression versus low HDAC2 was 32.3 versus 9.2 months (<i>P</i> = .004) for all patients and 43.3 versus 25.1 months for patients with RCC (<i>P</i> = .09). Exceptional responders had lower kynurenine levels both pre- and post-treatment (<i>P</i> = .002, <i>P</i> < .001, respectively). HDAC2 and kynurenine expression levels were inversely correlated (<i>P</i> = .02).</p><p><strong>Conclusion: </strong>Abexinostat added to pazopanib shows extended tolerability and long-term responses and survival. PBMC HDAC2 levels, the abexinostat target, are relevant predictors of response. In addition, metabolomic assessment points to kynurenine as a predictor for exceptional response to combined VEGF plus HDAC inhibition.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400328"},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604540","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":"DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance.","authors":"Kathleen Conway, Sharon N Edmiston, Amanda Vondras, Allison Reiner, David L Corcoran, Ronglai Shen, Eloise A Parrish, Honglin Hao, Lan Lin, Jessica M Kenney, Gbemisola Ilelaboye, Caroline E Kostrzewa, Pei Fen Kuan, Klaus J Busam, Cecilia Lezcano, Tim K Lee, Eva Hernando, Paul B Googe, David W Ollila, Stergios Moschos, Ivan Gorlov, Christopher I Amos, Marc S Ernstoff, Anne E Cust, James S Wilmott, Richard A Scolyer, Graham J Mann, Ismael A Vergara, Jennifer Ko, Judy R Rees, Shaofeng Yan, Eduardo Nagore, Marcus Bosenberg, Bonnie Gould Rothberg, Iman Osman, Jeffrey E Lee, Yvonne Saenger, Paul Bogner, Cheryl L Thompson, Meg Gerstenblith, Sheri L Holmen, Pauline Funchain, Elise Brunsgaard, Natalie D Depcik-Smith, Li Luo, Tawny Boyce, Irene Orlow, Colin B Begg, Marianne Berwick, Nancy E Thomas","doi":"10.1200/PO-24-00375","DOIUrl":"https://doi.org/10.1200/PO-24-00375","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with stage II and III cutaneous primary melanoma vary considerably in their risk of melanoma-related death. We explore the ability of methylation profiling to distinguish primary melanoma methylation classes and their associations with clinicopathologic characteristics and survival.</p><p><strong>Materials and methods: </strong>InterMEL is a retrospective case-control study that assembled primary cutaneous melanomas from American Joint Committee on Cancer (AJCC) 8th edition stage II and III patients diagnosed between 1998 and 2015 in the United States and Australia. Cases are patients who died of melanoma within 5 years from original diagnosis. Controls survived longer than 5 years without evidence of melanoma recurrence or relapse. Methylation classes, distinguished by consensus clustering of 850K methylation data, were evaluated for their clinicopathologic characteristics, 5-year survival status, and differentially methylated gene sets.</p><p><strong>Results: </strong>Among 422 InterMEL melanomas, consensus clustering revealed three primary melanoma methylation classes (MethylClasses): a CpG island methylator phenotype (CIMP) class, an intermediate methylation (IM) class, and a low methylation (LM) class. CIMP and IM were associated with higher AJCC stage (both <i>P</i> = .002), Breslow thickness (CIMP <i>P</i> = .002; IM <i>P</i> = .006), and mitotic index (both <i>P</i> < .001) compared with LM, while IM had higher N stage than CIMP (<i>P</i> = .01) and LM (<i>P</i> = .007). CIMP and IM had a 2-fold higher likelihood of 5-year death from melanoma than LM (CIMP odds ratio [OR], 2.16 [95% CI, 1.18 to 3.96]; IM OR, 2.00 [95% CI, 1.12 to 3.58]) in a multivariable model adjusted for age, sex, log Breslow thickness, ulceration, mitotic index, and N stage. Despite more extensive CpG island hypermethylation in CIMP, CIMP and IM shared similar patterns of differential methylation and gene set enrichment compared with LM.</p><p><strong>Conclusion: </strong>Melanoma MethylClasses may provide clinical value in predicting 5-year death from melanoma among patients with primary melanoma independent of other clinicopathologic factors.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400375"},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604533","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":"Neo-wt-<i>RAS</i> in ctDNA: Is It Worth Using Anti-EGFR Therapies?","authors":"Pasquale F Innominato, Abdoulaye Karaboué, Francis A Lévi","doi":"10.1200/PO-24-00628","DOIUrl":"https://doi.org/10.1200/PO-24-00628","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400628"},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604537","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":"KRASG12D-Mutated Metastatic Colorectal Cancer: Clinical, Molecular, Immunologic, and Prognostic Features of a New Emerging Targeted Alteration.","authors":"Roberto Moretto, Daniele Rossini, Sabina Murgioni, Paolo Ciracì, Vincenzo Nasca, Marco Maria Germani, Maria Alessandra Calegari, Guglielmo Vetere, Rossana Intini, Ada Taravella, Vittorio Studiale, Chiara Boccaccio, Alessandro Passardi, Emiliano Tamburini, Alberto Zaniboni, Lisa Salvatore, Filippo Pietrantonio, Sara Lonardi, Gianluca Masi, Chiara Cremolini","doi":"10.1200/PO.24.00329","DOIUrl":"https://doi.org/10.1200/PO.24.00329","url":null,"abstract":"<p><strong>Purpose: </strong>KRASG12D mutation (mut) occurs in about 10%-12% of metastatic colorectal cancer (mCRC). Recently, novel KRASG12D inhibitors have been developed and are currently under investigation in phase I/II clinical trials in solid tumors including mCRC. We aimed at performing a comprehensive characterization of clinical, molecular, immunologic, and prognostic features of KRASG12D-mutated mCRC to inform the design and the interpretation of future trials.</p><p><strong>Methods: </strong>We performed a pooled analysis of phase III TRIBE and TRIBE2 studies comparing 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/bevacizumab (bev) to doublets (5-fluorouracil, leucovorin, and oxaliplatin or 5-fluorouracil, leucovorin, and irinotecan)/bev.</p><p><strong>Results: </strong>One hundred and thirty-six (16%) of 854 patients with available KRASG12D mutational status were KRASG12D mutated. KRASG12D-mutated patients had more frequently right-sided primary tumor and were less likely to present liver-only metastases with respect to other RAS mutated and all-wild-type (wt) patients. Compared with the BRAFV600E-mutated group, KRASG12D-mutated patients had more frequently left-sided primary tumor, resected primary tumor at the time of diagnosis, and Eastern Cooperative Oncology Group performance status 0. KRASG12D-mutated patients had better prognosis than BRAFV600E-mutated and worse prognosis than all wt patients. No prognostic difference was evident between KRASG12D mut and other <i>RAS</i> mut patients overall or according to other specific <i>KRAS</i> or <i>NRAS</i> hotspot mutations. No interaction effect was observed between KRASG12D mut and the benefit provided by FOLFOXIRI/bev compared with doublets/bev. <i>PIK3CA</i> mut were reported more frequently among KRASG12D-mutated tumors compared with both other <i>RAS</i> mut and all wt.</p><p><strong>Conclusion: </strong>A detail estimation of KRASG12D mut mCRC patients' characteristics and expected outcomes may be useful when planning future studies in this subgroup. The high prevalence of PI3K/PTEN/Akt pathway activating alterations may affect the efficacy of targeted strategies.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400329"},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604534","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":"DNA Damage Response Alterations Predict for Neoadjuvant Chemotherapy Sensitivity in Muscle-Invasive Bladder Cancer: A Correlative Analysis of the SWOG S1314 Trial.","authors":"Gopa Iyer, Catherine M Tangen, Michal Sarfaty, Ashley M Regazzi, I-Ling Lee, Megan Fong, Woonyoung Choi, Colin P N Dinney, Thomas W Flaig, Ian M Thompson, Seth P Lerner, David J McConkey, Jonathan E Rosenberg","doi":"10.1200/PO.24.00287","DOIUrl":"https://doi.org/10.1200/PO.24.00287","url":null,"abstract":"<p><strong>Purpose: </strong>Alterations in DNA damage response (DDR) genes, including <i>ERCC2</i>, have been correlated with response to neoadjuvant cisplatin-based chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC). The SWOG 1314 (S1314) trial enrolled patients with MIBC who received one of two NAC regimens followed by radical cystectomy. We examined the prevalence of DDR alterations in NAC responders versus nonresponders and correlated DDR alteration status with response.</p><p><strong>Methods: </strong>Pretreatment tumor specimens from 179 evaluable patients underwent next-generation sequencing (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets assay). Associations were determined between any or only deleterious alterations within nine predefined DDR genes, or any alterations in <i>ERCC2</i>, and progression-free survival (PFS) and overall survival using Cox regression, and, in a subset of evaluable patients, pathologic response (complete response, pT0, or downstaging to <pT2) using logistic regression, adjusting for clinical stage and performance status.</p><p><strong>Results: </strong>Deleterious DDR alterations were detected in 41 (23%) of 179 patients. Of the 151 patients evaluable for pathologic response, patients with deleterious DDR alterations (n = 39) demonstrated a higher pathologic response rate than those without (odds ratio [OR], 3.24 [95% CI, 1.51 to 6.94]; <i>P</i> = .003). In 24 <i>ERCC2</i>-mutant patients, the OR for pT0 was 3.33 (95% CI, 1.35 to 8.22; <i>P</i> = .009) and for <pT2 was 2.33 (95% CI, 0.92 to 5.89; <i>P</i> = .073). The association between deleterious DDR alterations and PFS provided an estimate of hazard ratio, 0.54 (95% CI, 0.29 to 1.01; <i>P</i> = .053).</p><p><strong>Conclusion: </strong>Deleterious DDR alterations were associated with pathologic response following NAC in S1314. Functional validation of <i>ERCC2</i> and other DDR alterations is underway to help refine such alterations as biomarkers of NAC in patients with bladder cancer.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400287"},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582365","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":"CD8⁺ Tumor-Infiltrating Lymphocytes in Head and Neck Cancer: A Review.","authors":"Kevin J Contrera, Matthew E Spector, Liron Pantanowitz, Ibrahim M Abukhiran, Lazar Vujanovic, Theresa L Whiteside, Yvonne M Mowery, Dan P Zandberg, Shaum S Sriharan, Seungwon Kim, Christopher Wilke, Heath D Skinner, Jose P Zevallos, Robert L Ferris","doi":"10.1200/PO.24.00183","DOIUrl":"https://doi.org/10.1200/PO.24.00183","url":null,"abstract":"<p><p>CD8⁺ tumor-infiltrating lymphocytes (TILs) are increasingly used in oncology as a prognostic and predictive tool to guide patient management. This review summarizes current literature on CD8⁺ TILs in head and neck squamous cell carcinoma (SCC). Published meta-analyses and clinical trials evaluating CD8⁺ TILs were analyzed. Consistent positive associations between elevated CD8⁺ TILs and overall survival have been observed across head and neck sites. CD8⁺ TILs have been found to predict response to treatment, most commonly immunotherapy, but also chemoradiation. Numerous trials have shown that increased CD8⁺ TIL frequencies in pretreatment biopsies could identify patients likely to respond to neoadjuvant therapies. CD8⁺ TIL infiltration has also been elevated in responders both during and after treatment. However, wider adoption of CD8⁺ TIL quantification as a biomarker has been limited by the need for clinical validation and universal measurement guidelines for head and neck SCC, as there are for other malignancies. Measurement variability includes which tumor compartment is sampled, how TILs are quantified, and which cutoffs are clinically relevant. For several head and neck SCC, measurement of CD8⁺ TILs in the central or intratumoral compartment, followed by the stromal compartment, has been most consistently associated with survival. Future studies are needed to evaluate subpopulations of CD8⁺ TILs and biomarker-based treatment selection.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400183"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681772","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":"Characterization and Clinical Outcome of Philadelphia Chromosome-Positive AML in Thrombocytopenia-Absent Radius Syndrome.","authors":"Alejandro Villar-Prados, Arman Odabas, Joshua R Menke, Kerry Kingham, Gabriel N Mannis","doi":"10.1200/PO-24-00411","DOIUrl":"10.1200/PO-24-00411","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400411"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406407","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":"Fully Automated Artificial Intelligence Solution for Human Epidermal Growth Factor Receptor 2 Immunohistochemistry Scoring in Breast Cancer: A Multireader Study.","authors":"Savitri Krishnamurthy, Stuart J Schnitt, Anne Vincent-Salomon, Rita Canas-Marques, Eugenia Colon, Kanchan Kantekure, Marina Maklakovski, Wilfrid Finck, Jeanne Thomassin, Yuval Globerson, Lilach Bien, Giuseppe Mallel, Maya Grinwald, Chaim Linhart, Judith Sandbank, Manuela Vecsler","doi":"10.1200/PO.24.00353","DOIUrl":"10.1200/PO.24.00353","url":null,"abstract":"<p><strong>Purpose: </strong>The proven efficacy of human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate therapy for treating HER2-low breast cancers necessitates more accurate and reproducible HER2 immunohistochemistry (IHC) scoring. We aimed to validate performance and utility of a fully automated artificial intelligence (AI) solution for interpreting HER2 IHC in breast carcinoma.</p><p><strong>Materials and methods: </strong>A two-arm multireader study of 120 HER2 IHC whole-slide images from four sites assessed HER2 scoring by four surgical pathologists without and with the aid of an AI HER2 solution. Both arms were compared with high-confidence ground truth (GT) established by agreement of at least four of five breast pathology subspecialists according to ASCO/College of American Pathologists (CAP) 2018/2023 guidelines.</p><p><strong>Results: </strong>The mean interobserver agreement among GT pathologists across all HER2 scores was 72.4% (N = 120). The AI solution demonstrated high accuracy for HER2 scoring, with 92.1% agreement on slides with high confidence GT (n = 92). The use of the AI tool led to improved performance by readers, interobserver agreement increased from 75.0% for digital manual read to 83.7% for AI-assisted review, and scoring accuracy improved from 85.3% to 88.0%. For the distinction of HER2 0 from 1+ cases (n = 58), pathologists supported by AI showed significantly higher interobserver agreement (69.8% without AI <i>v</i> 87.4% with AI) and accuracy (81.9% without AI <i>v</i> 88.8% with AI).</p><p><strong>Conclusion: </strong>This study demonstrated utility of a fully automated AI solution to aid in scoring HER2 IHC accurately according to ASCO/CAP 2018/2023 guidelines. Pathologists supported by AI showed improvements in HER2 IHC scoring consistency and accuracy, especially for distinguishing HER2 0 from 1+ cases. This AI solution could be used by pathologists as a decision support tool for enhancing reproducibility and consistency of HER2 scoring and particularly for identifying HER2-low breast cancers.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400353"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406408","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":"Amplification of <i>MYC</i> and Its Enhancer Correlates With Genetic Ancestry in Lung Squamous Cell Carcinoma.","authors":"Sejal Jain, Xuechun Bai, Samyukta Mallick, Branden Kinghorn, Benjamin May, Alexandria G Yao, Diane Allen-Gipson, Xiaoyang Zhang, Brian S Henick, Fatemeh Momen-Heravi, Jian Carrot-Zhang, Alison M Taylor","doi":"10.1200/PO.24.00223","DOIUrl":"10.1200/PO.24.00223","url":null,"abstract":"<p><strong>Purpose: </strong>In lung squamous cell carcinoma (LUSC), Black patients show significantly higher incidence and lower overall survival than White patients. Although socioeconomic factors likely contribute to this survival disparity, genomic factors have yet to be elucidated in LUSC.</p><p><strong>Methods: </strong>Using 416 LUSC tumor samples in the Cancer Genome Atlas (TCGA), we assessed genomic and transcriptomic profiles by ancestry. We replicated our analyses in pan-cancer data from TCGA, the American Association of Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE), and Columbia University Medical Center.</p><p><strong>Results: </strong>We found increased <i>MYC</i> amplification, LUSC-specific <i>MYC</i> enhancer amplification, and chromosome arm 8q (chr8q) gain to be significantly associated with genetic AFR (African) ancestry in LUSC in TCGA. Furthermore, expression of <i>MYC</i> target genes was significantly enriched in AFR samples. Local ancestry analysis identified correlation of chr8q gain with AFR ancestry at the <i>MYC</i> locus in TCGA. We also found a significant correlation between chr8q and AFR ancestry in multiple cancer types and pan-cancer in TCGA. Similarly, in a pan-cancer subset of AACR GENIE data, we found a significant correlation between chr8q gain and race.</p><p><strong>Conclusion: </strong>Together, our data suggest that ancestry may influence amplification of not only <i>MYC</i> but also its enhancer in LUSC. They also suggest a role for genetic ancestry in chr8q aneuploidy in cancer. These studies further define and expand patients who may benefit from future anti-<i>MYC</i> therapeutic approaches.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400223"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500780","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}