Table 1.
Main findings contributed by Next Generation Sequencing (NGS) in endometrial cancers (ECs).
| Method | Samples | Main findings | Study |
|---|---|---|---|
| Low-pass whole genome sequencing | ECs and matched DNA from normal tissues or blood (n = 106 pairs) | Recurrent translocations of genes in WNT, EGFR–RAS–MAPK, PI(3)K, protein kinase A, retinoblastoma and apoptosis pathway. The most frequent translocations in the member of BCL family (BCL2, BCL7A, BCL9, and BCL2L11). |
Cancer Genome Atlas Research Network et al., 2013 |
| Whole exome sequencing | ECs and matched DNA from normal tissues or blood (n = 248 pairs) | Frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A, KRAS and novel mutations in ARID5B. Significant increase of transversion mutation frequency and novel hotspot mutations in POLE in a subset of endometrioid cancers. | |
| Whole exome sequencing | EC and matched DNA from blood (n = 13 pairs) | Mutation on ARID1A are associated with PI3K pathway activation. | Liang et al., 2012 |
| Whole exome sequencing | Uterine serous cancer and matched normal tissues (n = 13 pairs) | Mutation on chromatin-remodeling and ubiquitin ligase complex genes. | Le Gallo et al., 2012 |
| Whole exome sequencing | Uterine serous cancer and matched DNA from blood or tissue samples (n = 10 pairs) | Mutation on FBXW7 and amplification of CCNE1 locus (encodes cyclin E, substrate of FBXW7). | Kuhn et al., 2012 |
| Whole exome sequencing | Uterine serous cancer (n = 52) and matched DNA from blood (n = 34) | Mutation on SPOP, CDH4, TAF1, amplification of CCNE1 and loss of MBD3. | Zhao et al., 2013 |
| Targeted gene sequencing (nine genes) | Low-grade EEC (n = 276), grade 3 EEC (n = 30), serous (n = 37) and carcinosarcoma subtype (n = 42) | Distinct mutation frequency on PTEN and TP53 on low-grade EEC and grade 3 EEC. Significantly different mutations frequency on PTEN, ARID1A, PPP2R1A, TP53, and CTNNB1 between grade 3 EEC and serous carcinoma. | McConechy et al., 2012 |
| Targeted gene sequencing (seven genes) | EEC (n = 307) and ovarian endometrioid cancer (n = 33) | Distinct mutation profile in PTEN and CTNNB1. | McConechy et al., 2014 |
| Targeted gene sequencing (578 genes) | EC (n = 10) | Frequent mutations in PTEN (50%) and genes involved in the endometrial cancer-related molecular pathway including IL-7 signaling pathway. | Chang et al., 2016 |
| RNA sequencing | ECs (n = 333) | Three clusters; mitotic, hormonal and immunoreactive | Cancer Genome Atlas Research Network et al., 2013 |
| Small RNA sequencing | ECs (n = 367) | Six miRNA clusters significantly associated with MLH1 hypermethylation (miR-148a and miR-375), histology, grade (miR-21) and stage. | |
| RNA sequencing | Stage I EEC and adjacent normal tissues (n = 3 pairs) | First report on dysregulation of miRNAs (hsa-miR-196a-5p, hsa-miR-328-3p, hsa-miR-337-3p, and hsa-miR-99a-3p) in EC. | Xiong et al., 2014 |
| Small RNA sequencing | Normal, hyperplastic, and EC biopsies (n = 10 trios) | Definition of sncRNAs signature (1229 miRNAs, 10 piRNAs and three SnoRNAs) involved in neoplastic transformation. | Ravo et al., 2015 |
| Paired end RNA sequencing | EC with matched non-cancerous tissue (n = 9 pairs) | Significant upregulation of fusion gene TSNAX-DISC1 in EC which formed through splicing without chromosomal rearrangement. | Li et al., 2014 |
EEC, Endometrial endometrioid carcinoma; sncRNAs, Small non-coding RNAs; miRNAs, MicroRNAs; piRNAs, Piwi-interacting RNA; SnoRNAs, Small nucleolar RNAs.