A New CTSA Partnership to Translate an Oral Cancer Biomarker from Lab to Clinic

CTSA 建立新合作伙伴关系，将口腔癌生物标志物从实验室转化为临床

• 批准号: 8291650
• 负责人: S. CLAIBORNE JOHNSTON
• 金额: $ 49.27万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8291650
• 关键词: Academic Medical Centers; Basic Science; Biological Assay; Biological Markers; Biopsy; Cancer Patient; Cause of Death; Cells; Cervical; Cervical lymph node group; Cessation of life; Chromosomes; Chromosomes, Human, Pair 20; Clinic; Clinical; Clinical Investigator; Collection; DNA; DNA copy number; Data; Databases; Detection; Diagnostic; Dissection; Enrollment; Environment; Evaluation; Excision; Future; Genomics; Goals; Health; Incidence; Incisional Biopsy; Institution; Interdisciplinary Study; Laboratories; Laboratory Finding; Malignant neoplasm of cervix uteri; Malignant neoplasm of ovary; Measurement; Measures; Medical; Methods; Molecular; Molecular Profiling; Morbidity - disease rate; Neck; Neck Dissection; Neoplasm Metastasis; Nodal; Operative Surgical Procedures; Oral; Pathologic; Patients; Pilot Projects; Prevalence; Primary Neoplasm; Procedures; Protocols documentation; Recurrence; Research; Research Personnel; Resource Development; Resources; Retrospective Studies; Risk; Risk Assessment; Sampling; Specimen; Swab; Technology; Testing; Time; Tissues; Translating; Translational Research; Translations; Work; base; bench to bedside; clinical application; cohort; cost; lymph nodes; malignant mouth neoplasm; melanoma; molecular marker; mouth squamous cell carcinoma; outcome forecast; patient population; prospective; prototype; sample collection; tumor; validation studies

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, but not all oral SCCs metastasize. Nevertheless, almost all oral SCC patients undergo neck dissection, surgery to remove the cervical (neck) lymph nodes, at the time of surgery to remove the primary tumor, because there are currently no clinical, pathologic or molecular markers that reliably discriminate oral SCCs that are at risk for metastasis and those that are not. Recent studies in our laboratories distinguished 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 another independent retrospective study of oral SCC patients. 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. Here, we are proposing to translate these retrospective research findings into a test that could be used to identify patients at low risk of metastasis that would be suitable for use during the routine patient evaluation period prior to surgical removal of the tumor. We will develop a non-invasive assay for our DNA copy number signature (+3q, -8p, +8q, +20) that will use array CGH to measure copy number for chromosomes 3q, 8p, 8q and 20 and tumor genomic DNA obtained by brush biopsy of the patient's cancer prior to surgery. Our goal is to develop methods of procedure for sample collection (Aim 1) and copy number detection (Aim 2), as well as appropriately track and share information amongst the collaborators (Aim 3). This bench-to-bedside translational research will benefit from the CTSA resources and expertise of the collaborating CTSA-supported investigators and their institutions.

描述（由申请人提供）：在美国，死于口腔鳞状细胞癌（SCC）的人数多于黑素瘤、宫颈癌或卵巢癌，且发病率（尤其是年轻人）正在增加。颈部转移是主要的死亡原因，但不是所有的口腔鳞癌转移。然而，几乎所有口腔SCC患者在手术切除原发性肿瘤时都进行颈淋巴结清扫术，手术切除颈（颈）淋巴结，因为目前没有临床，病理或分子标记物可靠地区分有转移风险的口腔SCC和没有转移风险的口腔SCC。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3q 8 pq 20亚型，其特征在于存在一种或多种复发性拷贝数畸变，+3q、-8p、+8q和/或+20。另一种亚型（非3q 8 pq 20）缺乏这些拷贝数改变。非3q 8 pq 20亚型与低转移风险（7%）相关，而3q 8 pq 20亚型的转移率为46%。这一观察结果在另一项对口腔鳞癌患者的独立回顾性研究中得到了证实。因此，在这些基因座中的一个或多个基因座处的DNA拷贝数改变是识别处于低转移风险的患者组的生物标志物，这些患者可以避免切除颈部淋巴结所需的可能不必要的大手术。在这里，我们建议将这些回顾性研究结果转化为一种测试，可用于识别低转移风险的患者，适用于手术切除肿瘤前的常规患者评估期。我们将为我们的DNA拷贝数特征（+3q，-8p，+8q，+20）开发一种非侵入性测定，该测定将使用阵列CGH测量染色体3q，8 p，8 q和20的拷贝数以及手术前通过患者癌症刷检获得的肿瘤基因组DNA。我们的目标是开发样本收集（目标1）和拷贝数检测（目标2）的程序方法，以及在合作者之间适当地跟踪和共享信息（目标3）。这种从实验室到临床的转化研究将受益于CTSA的资源和合作CTSA支持的研究人员及其机构的专业知识。