Scholarlink

<p>Anal squamous cell carcinoma (aSCC) is a rare, predominantly HPV-driven cancer with limited treatment options. This study aimed to define its genomic landscape, identify actionable targets (AT), and highlight the clinical value of molecular profiling—especially liquid biopsy (LB)—based on Gustave Roussy’s (GR) experience. In this retrospective analysis, 1844 patients from the U.S. and France underwent tissue biopsy (TB, <i>n</i> = 1733) and/or LB (<i>n</i> = 140), analyzed using the FoundationOne®CDx or FoundationOne® Liquid CDx assays both comprehensive genomic profiling assays for solid tumors covering ~324 genes. Twenty-nine patients had paired TB/LB, and 44 LB patients formed the clinically annotated GR subgroup. HPV was detected in 86.6% of cases, predominantly HPV-16 (75.6%). High tumor mutational burden (≥10 mut/Mb) was found in 17.1% of patients; microsatellite instability was rare (1.7%). Frequent mutations included <i>PIK3CA</i> (34.5%), <i>KMT2D</i> (18.0%), <i>PTEN</i> (13.1%), <i>FBXW7</i> (12.9%), and <i>TP53</i> (12.0%). ATs were identified in <i>BRCA1/2, FGFR2/3, EGFR, KRAS, BRAF</i>, and <i>NRAS</i>. Mutation patterns varied by HPV subtype. LB showed high concordance with TB, including HPV detection. At GR, LB informed treatment decisions in 18.2% of cases. Four clinical examples illustrated LB-guided therapies. This largest-to-date aSCC cohort reinforces molecular profiling—especially LB—as a key tool for guiding personalized therapy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Comprehensive molecular landscape of anal squamous cell carcinoma: analysis of tissue and liquid biopsies from 1844 patients

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月24日

查看全文
  • Cristina Smolenschi,
  • Saumya D. Sisoudiya,
  • Antoine Hollebecque,
  • Smruthy Sivakumar,
  • Meagan Montesion,
  • Victor Euzen,
  • Valérie Boige,
  • Alice Boilève,
  • Marine Valery,
  • Isabelle Sourouille,
  • Arnaud Bayle,
  • Mihaela Aldea,
  • Julieta Elena Rodriguez,
  • Massimiliano Gelli,
  • Filippo Gustavo Dall’Olio,
  • Anthony Tarabay,
  • Thomas Pudlarz,
  • Rastislav Bahleda,
  • Alina Fuerea,
  • Léonor Benhaim,
  • Elena Fernandez de Sevilla,
  • Mohamed Bani,
  • Peggy Dartigues,
  • Simon Pernot,
  • Gautier Boillet,
  • Kristi Beshiri,
  • Christophe Massard,
  • Luc Friboulet,
  • Francesco Facchinetti,
  • Ludovic Lacroix,
  • Etienne Rouleau,
  • Fabrice Barlesi,
  • Michel Ducreux,
  • Antoine Italiano,
  • Radwa Sharaf,
  • Damien Vasseur

摘要

Anal squamous cell carcinoma (aSCC) is a rare, predominantly HPV-driven cancer with limited treatment options. This study aimed to define its genomic landscape, identify actionable targets (AT), and highlight the clinical value of molecular profiling—especially liquid biopsy (LB)—based on Gustave Roussy’s (GR) experience. In this retrospective analysis, 1844 patients from the U.S. and France underwent tissue biopsy (TB, n = 1733) and/or LB (n = 140), analyzed using the FoundationOne®CDx or FoundationOne® Liquid CDx assays both comprehensive genomic profiling assays for solid tumors covering ~324 genes. Twenty-nine patients had paired TB/LB, and 44 LB patients formed the clinically annotated GR subgroup. HPV was detected in 86.6% of cases, predominantly HPV-16 (75.6%). High tumor mutational burden (≥10 mut/Mb) was found in 17.1% of patients; microsatellite instability was rare (1.7%). Frequent mutations included PIK3CA (34.5%), KMT2D (18.0%), PTEN (13.1%), FBXW7 (12.9%), and TP53 (12.0%). ATs were identified in BRCA1/2, FGFR2/3, EGFR, KRAS, BRAF, and NRAS. Mutation patterns varied by HPV subtype. LB showed high concordance with TB, including HPV detection. At GR, LB informed treatment decisions in 18.2% of cases. Four clinical examples illustrated LB-guided therapies. This largest-to-date aSCC cohort reinforces molecular profiling—especially LB—as a key tool for guiding personalized therapy.