FISH assay identifying oral cancer patients at low risk of lymph node metastasis

FISH 检测可识别淋巴结转移风险较低的口腔癌患者

• 批准号: 8719677
• 负责人: Donna G Albertson
• 金额: $ 17.98万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-12 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8719677
• 关键词: Biological Assay; Biological Markers; Biopsy; Cancer Patient; Cause of Death; Cervical; Cervical lymph node group; Cessation of life; Chromosomes; Chromosomes, Human, Pair 20; Clinical; Collection; DNA copy number; Detection; Diagnostic; Dissection; Distant Metastasis; Evaluation; Excision; Fluorescent in Situ Hybridization; Incidence; Investigation; Label; Laboratories; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of ovary; Measurement; Medical; Methods; Molecular Profiling; Morbidity - disease rate; Neck; Neck Dissection; Neoplasm Metastasis; Office Visits; Operative Surgical Procedures; Oral; Pathologic; Patients; Primary Neoplasm; Recurrence; Risk; Risk Assessment; Sampling; Specimen; Techniques; Technology; Testing; Time; Work; base; cohort; cost; lymph nodes; malignant mouth neoplasm; melanoma; molecular marker; mouth squamous cell carcinoma; neoplastic cell; outcome forecast; prospective; research clinical testing; response; sample collection; sample fixation; treatment planning; tumor

DESCRIPTION (provided by applicant): In the USA, more people die from oral squamous cell carcinoma (SCC) than melanoma, cervical or ovarian cancer and the incidence, particularly in young people, is increasing. Neck metastasis is the primary cause of death; however, not all oral SCCs metastasize. Due to the current poor accuracy in detecting metastasis by clinical or radiographic examination prior to surgical removal of the primary cancer, neck dissection, surgery to remove the cervical (neck) lymph nodes is performed if the metastatic risk is >20% based on current risk assessment capability. Therefore, almost all oral SCC patients undergo a neck dissection which increases patient morbidity. Recent studies in our laboratories have discriminated two oral SCC subtypes with distinct molecular signatures and metastatic rates. One subtype, the 3q8pq20 subtype, is characterized by the presence of one or more of the recurrent copy number aberrations, +3q, - 8p, +8q and/or +20. The other subtype (non-3q8pq20) lacks these copy number alterations. The non-3q8pq20 subtype is associated with a low risk of metastasis (7%) compared to the 46% rate of metastasis in the 3q8pq20 subtype. This observation has been replicated in an independent oral SCC cohort. Thus, DNA copy number alterations at one or more of these loci is a biomarker identifying a group of patients at low risk for metastasis, who could be spared the potentially unnecessary major surgery required for removal of the cervical lymph nodes. In response to PA-09-158, we are proposing to develop our DNA copy number signature (+3q, -8p, +8q, +20) as a clinical test to identify the non-3q8pq20 subset of patients at low risk for metastasis. To this end, we will develop and validate a FISH-based assay to detect DNA copy number for chromosomes 3q, 8p, 8q and 20 that is suitable for analysis of lesional brush biopsies collected prior to surgery. Work will focus on sample collection (Aim 1) and copy number detection by FISH (Aim 2). We seek the combination of specimen collection technique and analysis technology that would be best suited for clinical implementation. The validated and optimized assay will be used to assess 3q8pq20 status in a subsequent multi-institutional prospective trial to establish the utility of this biomarker to identify patients who do not require a neck dissection.

描述（由申请人提供）：在美国，死于口腔鳞状细胞癌 (SCC) 的人数多于黑色素瘤、宫颈癌或卵巢癌，而且发病率（尤其是年轻人）正在增加。颈部转移是死亡的主要原因；然而，并非所有口腔鳞状细胞癌都会转移。由于目前在手术切除原发癌、颈清扫术之前通过临床或放射学检查检测转移的准确性较差，如果转移风险基于当前风险>20%，则进行颈（颈）淋巴结切除手术评估能力。因此，几乎所有口腔鳞状细胞癌患者都会接受颈清扫术，这增加了患者的发病率。我们实验室最近的研究区分了两种具有不同分子特征和转移率的口腔鳞状细胞癌亚型。一种亚型，即3q8pq20亚型，其特征在于存在一种或多种反复出现的拷贝数畸变：+3q、-8p、+8q和/或+20。另一种亚型（非 3q8pq20）缺乏这些拷贝数改变。与 3q8pq20 亚型的 46% 转移率相比，非 3q8pq20 亚型的转移风险较低 (7%)。这一观察结果已在独立的口腔 SCC 队列中得到重复。因此，这些基因座中一个或多个位点的 DNA 拷贝数改变是一种生物标志物，可识别一组转移风险较低的患者，这些患者可以避免切除颈部淋巴结所需的潜在不必要的大手术。为了响应 PA-09-158，我们建议开发 DNA 拷贝数特征（+3q、-8p、+8q、+20）作为临床测试，以识别转移风险低的非 3q8pq20 患者子集。为此，我们将开发并验证一种基于 FISH 的检测方法，用于检测染色体 3q、8p、8q 和 20 的 DNA 拷贝数，该方法适用于分析手术前收集的病变刷活检。工作重点是样本收集（目标 1）和 FISH 拷贝数检测（目标 2）。我们寻求最适合临床实施的标本采集技术和分析技术的结合。经过验证和优化的检测将用于在随后的多机构前瞻性试验中评估 3q8pq20 状态，以确定该生物标志物在识别不需要颈清扫术的患者方面的效用。