Departments of Pathology and Medicine, Massachusetts General Hospital; Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
Clin Cancer Res. 2013 Jan 15;19(2):480-90. doi: 10.1158/1078-0432.CCR-12-1842. Epub 2012 Nov 27.
Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland cancers for which cytotoxic chemotherapy has limited efficacy. We investigated whether genotyping analysis could detect novel tumor-specific mutations that would help direct SDC patient treatment using targeted agents.
We genotyped 27 SDC archival specimens from patients followed at Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary (Boston, MA) between 2000 and 2011. These included the tumors of 8 patients who were tested prospectively. Targeted mutational analysis of 13 clinically relevant cancer genes was conducted using SNaPshot multiplexed genotyping. FISH was conducted to detect HER2 gene amplification. Patient medical records and tumor histopathologic features were retrospectively reviewed.
Mutually exclusive genetic aberrations were detected in 15 of 27 (56%) tumors, including 2 (7%) mutations in BRAF, 5 (19%) mutations in PIK3CA, and 8 (30%) cases of HER2 gene amplification. To our knowledge, this is the first time that BRAF and PIK3CA mutations have been reported in this tumor type. Prospective clinical testing of 8 patients with SDC identified actionable genetic alterations in 6 tumors and influenced therapeutic decisions for all 6 patients.
SNaPshot molecular profiling identified novel genetic changes in SDCs, expanded the therapeutic options for patients with this rare tumor, and is changing SDC management at our institution. These findings highlight the importance of using broad-based genetic profiling to expedite the identification of effective-targeted therapies for patients with rare malignancies.
唾液腺癌（SDC）是一种罕见且侵袭性的唾液腺癌，细胞毒性化疗对此类癌症的疗效有限。我们研究了基因分型分析是否可以检测到新的肿瘤特异性突变，从而有助于通过靶向药物为 SDC 患者治疗提供指导。
我们对 2000 年至 2011 年间在马萨诸塞州综合医院和马萨诸塞州眼耳医院（波士顿，MA）接受治疗的 27 名 SDC 存档标本进行了基因分型。其中包括 8 名前瞻性检测患者的肿瘤。使用 SNaPshot 多重基因分型对 13 个临床相关癌症基因进行靶向突变分析。进行荧光原位杂交（FISH）以检测 HER2 基因扩增。回顾性审查患者的病历和肿瘤组织病理学特征。
在 27 个肿瘤中有 15 个（56%）检测到相互排斥的遗传异常，包括 2 个（7%）BRAF 突变，5 个（19%）PIK3CA 突变和 8 个（30%）HER2 基因扩增。据我们所知，这是首次在这种肿瘤类型中报道 BRAF 和 PIK3CA 突变。对 8 名 SDC 患者进行的前瞻性临床检测在 6 个肿瘤中发现了可操作的遗传改变，并影响了 6 名患者的治疗决策。
SNaPshot 分子谱分析确定了 SDC 中的新遗传变化，为这种罕见肿瘤的患者扩大了治疗选择，并正在改变我们机构的 SDC 管理方式。这些发现强调了使用广泛的遗传谱分析来加快确定罕见恶性肿瘤有效靶向治疗的重要性。
