scholarly journals Mutation analysis of a 10-gene panel for colorectal cancer in Huizhou, Guangdong Province of China

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110610
Author(s):  
Jun Li ◽  
Aihua Sun ◽  
Guofang Zhong ◽  
Ying He ◽  
Hailin Xiong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Single Gene ◽  
Gene Mutations ◽  
Clinical Information ◽  
Comprehensive Analysis ◽  
Gene Panel ◽  
Targeting Therapy ◽  
Three Samples ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Objective This study aimed to investigate the type and frequency of mutations in 10 genes in 85 colorectal cancer (CRC) patients in Huizhou and the guiding significance of targeted drug use. Methods The 10-gene panel next-generation sequencing (NGS) was used to assess genetic variants in 85 CRC patients from the Huizhou area combined with clinical information for a comprehensive analysis. Results Upon initial mutation testing, 68% (58/85) were positive. The mutation frequencies of these genes, including KRAS, PIK3CA, NRAS, ERBB2, BRAF, EGFR, and PDGFRA, were 51%, 20%, 5%, 4%, 4%, 1%, and 1%, respectively. Overall, 29 mutation types were detected from seven genes. More mutations were detected in more advanced cancers. There were three samples with multiple mutations of a single gene, including KRAS (n = 2) and ERBB2 (n = 2), 12 samples with multiple mutations of double genes, including KRAS/PIK3CA (n = 10), BRAF/PIK3CA (n = 1), and NRAS/PIK3CA (n = 1), and one sample with multiple mutations of three genes, including ERBB2/KRAS/PIK3CA (n = 1). Theoretically, 27 patients could receive targeted treatment. During the actual treatment, 10 patients received bevacizumab, cetuximab, or fruquintinib with no progression ranging from 12 to 24 months. Conclusion Gene mutations detected by a 10-gene panel were useful for targeting therapy of CRC in Huizhou.

scholarly journals Less frequently mutated genes in colorectal cancer: evidences from next-generation sequencing of 653 routine cases

2016 ◽  
Vol 69 (9) ◽  
pp. 767-771 ◽  
Author(s):  
Umberto Malapelle ◽  
Pasquale Pisapia ◽  
Roberta Sgariglia ◽  
Elena Vigliar ◽  
Maria Biglietto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Somatic Mutations ◽  
Gene Mutations ◽  
Next Generation ◽  
Genomic Landscape ◽  
Next Generation Sequencing Ngs ◽  
Pcr Targeting ◽  
Diagnostic Setting ◽  
Generation Sequencing

AimsThe incidence of RAS/RAF/PI3KA and TP53 gene mutations in colorectal cancer (CRC) is well established. Less information, however, is available on other components of the CRC genomic landscape, which are potential CRC prognostic/predictive markers.MethodsFollowing a previous validation study, ion-semiconductor next-generation sequencing (NGS) was employed to process 653 routine CRC samples by a multiplex PCR targeting 91 hotspot regions in 22 CRC significant genes.ResultsA total of 796 somatic mutations in 499 (76.4%) tumours were detected. Besides RAS/RAF/PI3KA and TP53, other 12 genes showed at least one mutation including FBXW7 (6%), PTEN (2.8%), SMAD4 (2.1%), EGFR (1.2%), CTNNB1 (1.1%), AKT1 (0.9%), STK11 (0.8%), ERBB2 (0.6%), ERBB4 (0.6%), ALK (0.2%), MAP2K1 (0.2%) and NOTCH1 (0.2%).ConclusionsIn a routine diagnostic setting, NGS had the potential to generate robust and comprehensive genetic information also including less frequently mutated genes potentially relevant for prognostic assessments or for actionable treatments.

Clinicopathological and genomic characteristics of POLE-mutated colorectal cancer in a Chinese population.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15531-e15531
Author(s):  
Xuhui Zhang ◽  
Xicheng Wang ◽  
Ying Xin ◽  
Yuezong Bai ◽  
Jian Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chinese Population ◽  
Gene Mutations ◽  
Metastatic Colon Cancer ◽  
Wild Type ◽  
Tumor Mutational Burden ◽  
Dna Replication And Repair ◽  
Colorectal Cancer Patients ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

e15531 Background: DNA polymerase ε (POLE) is essential for proofreading and fidelity in DNA replication and repair. Previous studies found that mutation in POLE associated with higher tumor mutational burden (TMB), which is an approved biomarker for immunotherpy in solid tumors. However, the clinicopathological and mutational analyses of POLE-mutated colorectal cancer in a large Chinese population have not yet been reported. Methods: Hybrid capture-based next-generation sequencing (NGS) were performed in 4628 samples of colorectal tumors and matched normal pairs in a CAP/CLIA-approved laboratory (3DMed). NGS testing for gene mutations, TMB and MSI was implemented. Results: Of 4628 colorectal cancer patients, POLE mutations were observed in 67 patients (1.45%). A total of 11 different POLE mutations were identified, mostly associated with exonucleas domain. P286R(32,0.69%), V411L(13,0.28%), A456P(7,0.15%), S459F(3,0.06%) and S297F(3,0.06%) were the most frequently mutated sites of POLE. We also detected 1 V758L and 1 W1130R mutation outside the exonuclease domain in separate cases. Among the 4628 patients, 2157 patients were detectable for TMB by NGS panel, including 2128 POLE wild type and 29 POLE mutation patients. The TMB of patients with POLE mutations was significantly higher than that in wide type POLE tumors (mean TMB 252.3 vs 13.4 muts/Mb, P ＜0.0001). All the 29 POLE-mutated patients were TMB-H (≥10 muts/Mb) and 28 of them were MSS. A MSS patient with metastatic colon cancer harboring A456P POLE mutation responsed well to the immunotherpy and achieved a partial response. Conclusions: Our results realved a remarkable positive correlation between POLE mutation and TMB level in a Chinese colorectal cancer population, which suggests POLE gene will be a promising biomarker of immunotherpy for MSS colorectal tumor.[Table: see text]

scholarly journals Jervell and Lange-Nielsen Syndrome due to a Novel Compound Heterozygous KCNQ1 Mutation in a Chinese Family

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yue Qiu ◽  
Sen Chen ◽  
Xia Wu ◽  
Wen-Juan Zhang ◽  
Wen Xie ◽  
...  
Keyword(s):  
Deaf Child ◽  
Gene Mutations ◽  
Deaf Children ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Qtc Interval ◽  
Cardiac Events ◽  
Life Threatening ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Jervell and Lange-Nielsen syndrome (JLNS) is a rare but severe autosomal recessive disease characterized by profound congenital deafness and a prolonged QTc interval (greater than 500 milliseconds) in the ECG waveforms. The prevalence of JLNS is about 1/1000000 to 1/200000 around the world. However, exceed 25% of JLNS patients suffered sudden cardiac death with kinds of triggers containing anesthesia. Approximately 90% of JLNS cases are caused by KCNQ1 gene mutations. Here, using next-generation sequencing (NGS), we identified a compound heterozygosity for two mutations c.1741A>T (novel) and c.477+5G>A (known) in KCNQ1 gene as the possible pathogenic cause of JLNS, which suggested a high risk of cardiac events in a deaf child. The hearing of this patient improved significantly with the help of cochlear implantation (CI). But life-threatening arrhythmias occurred with a trigger of anesthesia after the end of the CI surgery. Our findings extend the KCNQ1 gene mutation spectrum and contribute to the management of deaf children diagnosed with JLNS for otolaryngologists (especially cochlear implant teams).

scholarly journals Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP)

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3487
Author(s):  
Shih-Ching Chang ◽  
Anna Fen-Yau Li ◽  
Pei-Ching Lin ◽  
Chun-Chi Lin ◽  
Hung-Hsin Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Gene Mutations ◽  
Proximal Colon ◽  
Tnm Stage ◽  
Cpg Island Methylator Phenotype ◽  
Kras Mutations ◽  
Methylator Phenotype ◽  
Next Generation Sequencing Ngs ◽  
Mutation Spectra

Background: The 5’-C-phosphate-G-3’ island methylator phenotype (CIMP) is a specific phenotype of colorectal cancer (CRC) associated with microsatellite instability-high (MSI-high) tumors. Methods: In this study, we determined the CIMP status using eight methylation markers in 92 MSI-high CRC patients after excluding five germline mismatch repair (MMR) gene mutations analyzed by next-generation sequencing (NGS) and confirmed by Sanger sequencing. The mutation spectra of 22 common CRC-associated genes were analyzed by NGS. Results: Of the 92 sporadic MSI-high tumors, 23 (25%) were considered CIMP-high (expressed more than 5 of 8 markers). CIMP-high tumors showed proximal colon preponderance and female predominance. The mutation profiles of CIMP-high tumors were significantly different from those of CIMP-low or CIMP-0 tumors (i.e., higher frequencies of BRAF, POLD1, MSH3, and SMAD4 mutations but lower frequencies of APC, TP53, and KRAS mutations). Multivariate analysis demonstrated that tumor, node, metastasis (TNM) stage was the independent prognostic factor affecting overall survival (OS). Among the MSI-high cases, the CIMP status did not impact the outcome of patients with MSI-high tumors. Conclusions: Only TNM stage was a statistically significant predictor of outcomes independent of CIMP profiles in MSI-high CRC patients. Sporadic MSI-high CRCs with different mechanisms of carcinogenesis have specific mutation profiles and clinicopathological features.

scholarly journals Methylmalonic Acidemia with Novel MUT Gene Mutations

2017 ◽  
Vol 2017 ◽  
pp. 1-2
Author(s):  
Inusha Panigrahi ◽  
Savita Bhunwal ◽  
Harish Varma ◽  
Simranjeet Singh
Keyword(s):  
Sanger Sequencing ◽  
Gene Mutations ◽  
Methylmalonic Acidemia ◽  
Feeding Problems ◽  
Novel Variants ◽  
Mut Gene ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Poor Weight Gain

A 5-year-old boy presented with recurrent episodes of fever, feeding problems, lethargy, from the age of 11 months, and poor weight gain. He was admitted and evaluated for metabolic causes and diagnosed as having methylmalonic acidemia (MMA). He was treated with vit B12 and carnitine supplements and has been on follow-up for the last 3 years. Mutation analysis by next generation sequencing (NGS), supplemented with Sanger sequencing, revealed two novel variants in the MUT gene responsible for MMA in exon 5 and exon 3, respectively. Recently he developed dystonic movements including orofacial dyskinesia. With advent of NGS, judicious use of NGS with Sanger sequencing can help identify causative possibly pathogenic mutations.

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