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，与黑色素瘤，宫颈癌或卵巢癌相比，死于口腔鳞状细胞癌（SCC）的人数更多，而且发病率，尤其是在年轻人中，正在增加。颈部转移是死亡的主要原因。但是，并非所有口服SCC转移。由于目前通过临床或放射学检查检测转移的准确性较差，然后在手术去除原发性癌症之前，颈部解剖，手术以去除颈椎（颈）淋巴结，如果转移性风险基于当前的风险评估能力，则进行the症淋巴结。因此，几乎所有的口服SCC患者都进行了颈部解剖，从而增加了患者的发病率。在我们的实验室中，最近的研究歧视了两种具有不同分子特征和转移率的口服SCC亚型。一种亚型，即3Q8PQ20亚型，其特征是存在一个或多个经常性拷贝数畸变， +3Q，-8p， +8q和/or +20。其他亚型（非3Q8PQ20）缺少这些拷贝数更改。非3Q8PQ20亚型与转移的风险低有关（7％），而3Q8PQ20亚型的转移率为46％。该观察结果已在独立的口服SCC队列中复制。因此，这些基因座中一个或多个的DNA拷贝数改变是一种生物标志物，识别一组患者的转移风险较低的患者，这些患者可能会幸免于去除宫颈淋巴结所需的潜在不必要的重大手术。为了响应PA-09-158，我们提议开发我们的DNA拷贝数签名（ +3Q，-8p， +8q，+20）作为临床测试，以鉴定非3Q8PQ20的非3Q8PQ20子集的转移风险较低的患者。为此，我们将开发和验证基于鱼类的测定法，以检测染色体3Q，8P，8Q和20的DNA拷贝数，适合分析手术前收集的病变刷活检。工作将集中于样品收集（AIM 1）和FISH（AIM 2）的拷贝数检测。我们寻求最适合临床实施的标本收集技术和分析技术的组合。经过验证和优化的测定将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的实用性，以识别不需要颈部剖析的患者。