A KRT6A and a Novel KRT16 Gene Mutations in Chinese Patients with Pachyonychia Congenita

Abstract Background Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. Methods Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated. Results The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. Conclusions This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.

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Morphological and Genetic Heterogeneity of Synchronous Multifocal Lung Adenocarcinoma in a Chinese Cohort

10.21203/rs.3.rs-77421/v1 ◽

2020 ◽

Author(s):

Donglin Zhu ◽

Dan Cao ◽

Minghong Shen ◽

Jinghuan Lv

Keyword(s):

Lung Cancer ◽

Primary Lung Cancer ◽

Gene Mutations ◽

Tumor Location ◽

Chinese Patients ◽

Molecular Testing ◽

Additional Tool ◽

Molecular Features ◽

Pathologic Features ◽

Genotypic Analysis

Abstract Background: Synchronous multifocal lung cancer (SMLC) is seen with increasing frequency in clinical practice globally. Because of innate variation in clinical management and outcome, it is vital to distinguish properly between synchronous multifocal primary lung cancer (SMPLC) and intrapulmonary metastasis (IM). The pathologic features and principal classification criteria of multifocal lung cancer remain unclear. Methods: We have collected a unique cohort of Chinese patients with SMLC, and fully explored the morphologic, immunohistochemical, and molecular features of the disease. Twenty-one SMLC patients with a total of 50 tumors were included in our study. The pathological features presented by these cases were analyzed, including tumor location, tumor size, pathological types, predominant pattern of adenocarcinoma, and immunohistochemical staining. We undertook molecular testing of nine driver oncogenes associated with lung cancer, including EGER, KRAS, BRAF, NRAS, ALK, ROS1, RET, HER2, and PIK3CA. Results: According to Martini-Melamed classification and refined standard, 8 and 17 cases were considered as SMPLC respectively. Gene mutations were identified in 18 tumors (36%). There were 12 patients had different gene mutations. Conclusions: We demonstrate that conventional morphological assessment is not sufficient to establish clearly the clonal relationship of SMPLC. Instead the evaluation of histological subtypes, including non-mucinous adherent components, is required. Multiplex genotypic analysis may also prove a useful additional tool.

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Novel Frizzled-4 Gene Mutations in Chinese Patients With Familial Exudative Vitreoretinopathy

Archives of Ophthalmology ◽

10.1001/archophthalmol.2010.240 ◽

2010 ◽

Vol 128 (10) ◽

pp. 1341 ◽

Cited By ~ 16

Author(s):

Li-Yun Jia

Keyword(s):

Gene Mutations ◽

Chinese Patients ◽

Familial Exudative Vitreoretinopathy

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Simultaneous detection of expression and gene mutations of HER2/neu in Chinese patients with gastric cancer

Oncology Letters ◽

10.3892/ol_00000099 ◽

2010 ◽

Vol 1 (3) ◽

pp. 559-563 ◽

Cited By ~ 2

Author(s):

XIULI ZhANG ◽

JIANHUI QU ◽

GANG SUN ◽

JING YANG ◽

YUNSHENG YANG

Keyword(s):

Gastric Cancer ◽

Simultaneous Detection ◽

Gene Mutations ◽

Chinese Patients

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Cross-Sectional Study in a Large Cohort of Chinese Patients With GJB1 Gene Mutations

Frontiers in Neurology ◽

10.3389/fneur.2020.00690 ◽

2020 ◽

Vol 11 ◽

Author(s):

Xiaoxuan Liu ◽

Xiaohui Duan ◽

Yingshuang Zhang ◽

Aping Sun ◽

Dongsheng Fan

Keyword(s):

Gene Mutations ◽

Cross Sectional Study ◽

Large Cohort ◽

Chinese Patients ◽

Sectional Study ◽

Cross Sectional

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NEMO Gene Mutations in Chinese Patients With Incontinentia Pigmenti

Journal of the Formosan Medical Association ◽

10.1016/s0929-6646(10)60042-3 ◽

2010 ◽

Vol 109 (3) ◽

pp. 192-200 ◽

Cited By ~ 9

Author(s):

Pa-Fan Hsiao ◽

Shuan-Pei Lin ◽

Shu-Shien Chiang ◽

Yu-Hung Wu ◽

Hsiu-Chin Chen ◽

...

Keyword(s):

Gene Mutations ◽

Chinese Patients ◽

Incontinentia Pigmenti

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Searching for CDH1 gene mutations in early-onset diffuse gastric cancer in Chinese patients.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.23 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 23-23

Author(s):

Xu Yanjun ◽

Cao Wenming ◽

Xu Qi ◽

Guo Jianmin ◽

Wang Xinbao ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Lymph Node ◽

Gene Mutations ◽

Germline Mutations ◽

Chinese Patients ◽

Diffuse Gastric Cancer ◽

Cdh1 Gene ◽

Node Metastasis ◽

Cdh1 Mutation

23 Background: CDH1 germline mutations are found to be associated with the development of hereditary diffuse gastric cancer (HDGC) and the early-onset diffuse gastric cancer (EODGC). But the impact of CDH1 gene mutations and large deletions on HDGC and EODGC has not been fully determined in Asians. Although the incidence of gastric cancer is relatively high in China, the detection rate of CDH1 germline mutations in Chinese patients with EODGC is rare compared to that in European patients. Methods: We investigated the mutation status of the CDH1 gene in 57 Chinese EODGC patients younger than 40 years old who met the clinical criteria for HDGC. Polymerase chain reaction-direct sequencing was performed, and multiplex ligation-dependent probe amplification (MLPA) was used to evaluate the patients with negative sequencing results. Associations between mutation, clinicopathologic, and overall survival data were analyzed by SPSS 19. Results: The germline mutations of CDH1gene were identified in 51 (89.5%) of the 57 EODGC patients. The nonsense mutation in exon 13 (c.2200T>C, p.Ala692*) occurred in fourty-six EODGC patients. The missense mutations were detected in twenty patients (Eighteen in exon 5: c.778G>C, p.Glu218Asp; Two in exon 12: c.2012C>G, p.Leu630Val). No deletion or duplication in any patient. Most of the patients carrying the CDH1 mutation in exon 13 had lymph node metastasis when compared with patients lacking CDH1 mutation (87.2% vs 60.0%) ( P < 0.05 ). EODGC patients, lacking germline CDH1 alterations, showed a longer median overall survival (mOS) than patients carrying CDH1 mutation in exon 13 ( P < 0.05 ). Moreover, the presence of CDH1 mutation in exon 13 was associated with the incidence of neural invasion ( P < 0.05 ). Conclusions: This study reveals novel CDH1 mutations in Chinese EODGC patients which had been poorly investigated. The presence of CDH1 mutation in EODGC patients may result in lymph node metastasis and poor prognosis. More research is needed to determine additional genetic targets that trigger EODGC.

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