可能个性化护理的 SNaPshot：妇科癌症的分子诊断。
A SNaPshot of potentially personalized care: Molecular diagnostics in gynecologic cancer.
机构信息
Division of Hematology Oncology, Yawkey 9-064, Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114, United States.
Division of Hematology Oncology, Yawkey 9-064, Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114, United States.
出版信息
Gynecol Oncol. 2016 Apr;141(1):108-12. doi: 10.1016/j.ygyno.2016.02.032.
BACKGROUND
Genetic abnormalities underlie the development and progression of cancer, and represent potential opportunities for personalized cancer therapy in Gyn malignancies.
METHODS
We identified Gyn oncology patients at the MGH Cancer Center with tumors genotyped for a panel of mutations by SNaPshot, a CLIA approved assay, validated in lung cancer, that uses SNP genotyping in degraded DNA from FFPE tissue to identify 160 described mutations across 15 cancer genes (AKT1, APC, BRAF, CTNNB1, EGFR, ERBB2, IDH1, KIT, KRAS, MAP2KI, NOTCH1, NRAS, PIK3CA, PTEN, TP53).
RESULTS
Between 5/17/10 and 8/8/13, 249 pts consented to SNaPshot analysis. Median age 60 (29-84) yrs. Tumors were ovarian 123 (49%), uterine 74(30%), cervical 14(6%), fallopian 9(4%), primary peritoneal 13(5%), or rare 16(6%) with the incidence of testing high grade serous ovarian cancer (HGSOC) halving over time. SNaPshot was positive in 75 (30%), with 18 of these (24%) having 2 or 3 (n=5) mutations identified. TP53 mutations are most common in high-grade serous cancers yet a low detection rate (17%) was likely related to the assay. However, 4 of the 7 purely endometrioid ovarian tumors (57%) harbored a p53 mutation. Of the 38 endometrioid uterine tumors, 18 mutations (47%) in the PI3Kinase pathway were identified. Only 9 of 122 purely serous (7%) tumors across all tumor types harbored a 'drugable' mutation, compared with 20 of 45 (44%) of endometrioid tumors (p<0.0001). 17 pts subsequently enrolled on a clinical trial; all but 4 of whom had PIK3CA pathway mutations. Eight of 14 (47%) cervical tumors harbored a 'drugable' mutation.
CONCLUSION
Although SNaPshot can identify potentially important therapeutic targets, the incidence of 'drugable' targets in ovarian cancer is low. In this cohort, only 7% of subjects eventually were treated on a relevant clinical trial. Geneotyping should be used judiciously and reflect histologic subtype and available platform.
背景
遗传异常是癌症发生和发展的基础，代表了妇科恶性肿瘤个体化癌症治疗的潜在机会。
方法
我们在 MGH 癌症中心确定了患有肿瘤的妇科肿瘤患者，这些肿瘤通过 SNaPshot 进行了一组突变的基因分型，SNaPshot 是一种 CLIA 批准的检测方法，已在肺癌中得到验证，该方法使用 SNP 基因分型在来自 FFPE 组织的降解 DNA 中鉴定 15 个癌症基因（AKT1、APC、BRAF、CTNNB1、EGFR、ERBB2、IDH1、KIT、KRAS、MAP2KI、NOTCH1、NRAS、PIK3CA、PTEN、TP53）中的 160 个描述性突变。
结果
在 2010 年 5 月 17 日至 2013 年 8 月 8 日期间，有 249 名患者同意进行 SNaPshot 分析。中位年龄为 60 岁（29-84 岁）。肿瘤为卵巢 123 例（49%）、子宫 74 例（30%）、宫颈 14 例（6%）、输卵管 9 例（4%）、腹膜 13 例（5%）或罕见 16 例（6%），检测到的高级别浆液性卵巢癌（HGSOC）的发生率随时间减半。SNaPshot 阳性率为 75%（30%），其中 18 例（24%）有 2 或 3 个（n=5）突变。TP53 突变在高级别浆液性癌症中最为常见，但检测率较低（17%），可能与检测方法有关。然而，7 例纯子宫内膜样卵巢肿瘤中有 4 例（57%）存在 p53 突变。在 38 例子宫内膜样子宫肿瘤中，鉴定出 18 个（47%）PI3K 通路突变。在所有肿瘤类型中，仅 122 例纯浆液性肿瘤中有 9 例（7%）存在“可治疗”突变，而在 45 例子宫内膜样肿瘤中有 20 例（44%）（p<0.0001）。17 名患者随后参加了临床试验；除 4 名患者外，所有患者均有 PI3K 通路突变。14 例宫颈肿瘤中有 8 例（47%）存在“可治疗”突变。
结论
尽管 SNaPshot 可以识别潜在的重要治疗靶点，但卵巢癌中“可治疗”靶点的发生率较低。在本队列中，最终只有 7%的患者在相关临床试验中接受了治疗。基因分型应谨慎使用，并反映组织学亚型和可用平台。
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