Human Whole Exome Sequencing

Sampling & Sequencing Strategy:

Sampling：
• 108 newly collected sGBM patient samples from AGGA
• 80 published datasets

Sequencing Strategy:
• Human whole exome sequencing, targeted region sequencing, and mRNA sequencing on Illumina HiSeq platform

Results & Conclusion:

By studying the mutational landscape (Figure 1) of 188 sGBMs, this study shows significant enrichment of TP53 mutations, somatic hypermutation, MET-exon-14-skipping (METex14), PTPRZ1-MET (ZM) fusions, and MET amplification. Strikingly, METex14 frequently co-occurs with ZM fusion and subsequent studies show that METex14 promotes glioma progression by prolonging MET activity. In addition, this study demonstrated the safety and efficacy of PLB-1001 (a MET-specific inhibitor) in patient treatment. Taken together, this paper described a comprehensive somatic mutation landscape of sGBM and provided a MET-targeted therapy for precision neuro-oncology.

Sampling & Sequencing Strategy:

Sampling：
• 182 Chinese primary HCC samples

Sequencing Strategy:
• Human whole genome sequencing (49 cases), whole exome sequencing (18 cases), and targeted region sequencing (115 cases) on Illumina platforms (PE150)

Results & Conclusion:

By using WGS, this study described the genomic landscape, including somatic SNVs/InDels, CNVs and SVs, and identified five prominent mutational signatures in 49 Chinese patients with HCC (Figure 2). Through WGS, WES, and targeted sequencing of 182 primary HCC samples, the results suggest that WNK2, RUNX1T1, CTNNB1, TSC1, and TP53 may play roles in HCC invasion and metastasis, and that WNK2 had the most significant difference in mutation frequency (Figure 3). Biofunctional investigations revealed a tumor-suppressor role for WNK2; its inactivation led to ERK1/2 signaling activation in HCC cells, tumor-associated macrophage infiltration, and tumor growth and metastasis. This study describes the genomic events that characterize Chinese HCCs and identify WNK2 as a driver of HCC that was associated with early tumor recurrence after curative resection.

Sampling:

• 75 patients (15 with H-ChC, 32 with HCC, and 28 with iCCA)
• 21 samples (HCC, iCCA, and adjacent noncancerous tissues) from seven H-ChC patients

Sequencing Strategy:

• Human whole exome sequencing on Illumina platform (PE150)

Results & Conclusion:

Whole exome sequencing analysis suggest a monoclonal origin (Figure 4) of H-ChC, which may promote the molecular classification of primary liver cancer on the basis of cell origin. In addition, the substantial intratumor heterogeneity (Figure 5) noted in H-ChC suggests that further multiregional sequencing analysis is necessary to find the common driver mutations that play an important role in carcinogenesis. This knowledge can be used to improve the precision and effectiveness of target drug selection.