Mutations in genes such as KRAS, NRAS, BRAF and PIK3CA have become an important part of colorectal carcinoma evaluation. The aim of this study was to screen for mutations in these genes in Chinese patients with colorectal cancer (CRC) and to explore their correlations with certain clinicopathological parameters. We tested mutations in the KRAS (exons 2, 3 and 4), NRAS (exons 2, 3 and 4), PIK3CA (exon 20) and BRAF (exon 15) genes using reverse transcriptase-polymerase chain reaction (RT-PCR) and Sanger sequencing in a large cohort of 1,110 Chinese CRC patients who underwent surgical resection at one of three major teaching hospitals located in different regions of China. The prevalence rates of KRAS, NRAS, BRAF and PIK3CA mutations were 45.4%, 3.9%, 3.1% and 3.5%, respectively. Mutant KRAS was associated with the mucinous subtype and greater differentiation, while mutant BRAF was associated with right-sided tumors and poorer differentiation. Our results revealed differences in the genetic profiles of KRAS, NRAS, PIK3CA and BRAF at mutation hotspots between Chinese CRC patients and those of Western countries, while some of these gene features were shared among patients from other Asian countries.
3 January 2018 in Journal of Cardiovascular Magnetic Resonance
Cardiac impairment is associated with high morbidity and mortality in immunoglobulin light chain (AL) type amyloidosis, for which early identification and risk stratification is vital. For myocardial tissue characterization, late gadolinium enhancement (LGE) is a classic and most commonly performed cardiovascular magnetic resonance (CMR) parameter. T1 mapping with native T1 and extracellular volume (ECV) are recently developed quantitative parameters. We aimed to investigate the prognostic value of native T1, ECV and LGE in patients with AL amyloidosis. Eighty-two patients (55.5 ± 8.5 years; 52 M) and 20 healthy subjects (53.2 ± 11.7 years; 10 M) were prospectively recruited. All subjects underwent CMR with LGE imaging and T1 mapping using a Modified Look-Locker Inversion-recovery (MOLLI) sequence on a 3 T scanner. Native T1 and ECV were measured semi-automatically using a dedicated CMR software. The left ventricular (LV) LGE pattern was classified as none, patchy, and global groups. Global LGE was considered when there was diffuse, transmural LGE in more than half of the short axis images. Follow-up was performed for all-cause mortality using Cox proportional hazards regression analysis and Kaplan-Meier survival curves. The patients demonstrated an increase in native T1 (1438 ± 120 ms vs. 1283 ± 46 ms, P = 0.001) and ECV (43.9 ± 10.9% vs. 27.0 ± 1.7%, P = 0.001) compared to healthy controls. Native T1, ECV and LGE showed significant correlation with Mayo Stage, and ECV and LGE showed significant correlation with echocardiographic E/E’ and LV ejection fraction. During the follow-up for a median time of 8 months, 21 deaths occurred. ECV ≥ 44.0% (hazard ratio [HR] 7.249, 95% confidence interval (CI) 1.751–13.179, P = 0.002) and global LGE (HR 4.804, 95% CI 1.971–12.926, P = 0.001) were independently prognostic for mortality over other clinical and imaging parameters. In subgroups with the same LGE pattern, ECV ≥ 44.0% remained prognostic (log rank P = 0.029). Median native T1 (1456 ms) was not prognostic for mortality (Tarone-Ware, P = 0.069). During a short-term follow-up, both ECV and LGE are independently prognostic for mortality in AL amyloidosis. In patients with a similar LGE pattern, ECV remained prognostic. Native T1 was not found to be a prognostic factor.
The BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations have been reported in papillary thyroid carcinoma (PTC). The aim of this retrospective cross-sectional study was to add further information regarding the prevalence of the BRAF V600E and TERT promoter mutations in Chinese PTC and their clinicopathological associations. We detected the BRAF V600E mutation and TERT promoter mutations in 455 Chinese PTC patients and analyzed the association of these mutations with several clinicopathological features. The BRAF V600E mutation was detected in 343 (75.4%) of 455 cases and was significantly associated with older age (p<0.001) and conventional subtype (p = 0.003). TERT promoter mutations were detected in 19 (4.4%) of 434 PTCs and were associated with older age (p<0.001), larger tumor size (p = 0.024), and advanced TNM stage(p<0.001). Of the 19 patients that were positive for TERT promoter mutations, 18 (94.7%) also harbored the BRAF V600E mutation. We determined the prevalence and clinicopathological associations of BRAF V600E and TERT promoter mutations in Chinese PTC patients. TERT promoter mutations but not the BRAF V600E mutation were associated with more advanced TNM stage upon diagnosis.