Seattle Children's Hospital, Seattle, WA, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Cancer Genet. 2022 Jan;260-261:46-52. doi: 10.1016/j.cancergen.2021.11.006. Epub 2021 Dec 5.
NTRK gene fusions are targetable oncogenic drivers independent of tumor type. Prevalence varies from highly recurrent in certain rare tumors to <1% in common cancers. The selective TRK inhibitor larotrectinib was shown to be highly active in adult and pediatric patients with tumors harboring NTRK gene fusions.
We examined the techniques used by local sites to detect tumor NTRK gene fusions in patients enrolled in clinical trials of larotrectinib. We also report the characteristics of the detected fusions in different tumor types.
The analysis included 225 patients with 19 different tumor types. Testing methods used were next-generation sequencing (NGS) in 196 of 225 tumors (87%); this was RNA-based in 96 (43%); DNA-based in 53 (24%); DNA/RNA-based in 46 (20%) and unknown in 1 (<1%); FISH in 14 (6%) and PCR-based in 12 (5%). NanoString, Sanger sequencing and chromosome microarray were each utilized once (<1%). Fifty-four different fusion partners were identified, 39 (72%) of which were unique occurrences.
The most common local testing approach was RNA-based NGS. Many different NTRK gene fusions were identified with most occurring at low frequency. This supports the need for validated and appropriate testing methodologies that work agnostic of fusion partners.
NTRK 基因融合是独立于肿瘤类型的可靶向致癌驱动因素。其患病率在某些罕见肿瘤中高度复发，而在常见癌症中则<1%。选择性 TRK 抑制剂拉罗替尼（larotrectinib）在携带 NTRK 基因融合的肿瘤的成年和儿科患者中表现出高度活性。
我们研究了在接受 larotrectinib 临床试验的患者中，当地机构用于检测肿瘤 NTRK 基因融合的技术。我们还报告了不同肿瘤类型中检测到的融合的特征。
分析包括 225 名患有 19 种不同肿瘤类型的患者。在 225 例肿瘤中的 196 例（87%）中使用了检测方法为下一代测序（NGS）；其中 96 例（43%）为基于 RNA 的；53 例（24%）为基于 DNA 的；46 例（20%）为 DNA/RNA 基于的，1 例（<1%）未知；14 例（6%）为 FISH，12 例（5%）为基于 PCR 的。NanoString、Sanger 测序和染色体微阵列各使用一次（<1%）。鉴定了 54 种不同的融合伙伴，其中 39 种（72%）为独特发生。
最常见的局部检测方法是基于 RNA 的 NGS。发现了许多不同的 NTRK 基因融合，大多数融合的发生率较低。这支持需要验证和适当的测试方法，这些方法应与融合伙伴无关。
