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

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.

Association of CDH1 mutation with prognosis in gastric adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15514-e15514
Author(s):  
Xiangyang Yu ◽  
Shimin Yang ◽  
Rong Du ◽  
Jingbo Zhang ◽  
Nan Fang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Stomach Cancer ◽  
Gastric Adenocarcinoma ◽  
Tumor Metastasis ◽  
Gene Mutations ◽  
Predictive Marker ◽  
Synonymous Mutations ◽  
Cdh1 Mutation ◽  
Gastric Cancer Patients

e15514 Background: Stomach cancer is a major cause of cancer death in East Asia. The purpose of this study was to find a predictive marker to estimate the prognosis of stomach cancer. Methods: In this study, a total of 34 gastric cancer patients receiving therapy in Tianjin Nankai Hospital were enrolled. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue sections, including carcinoma and pericarcinous tissues. Targeted regions of 549 cancer-associated genes were amplified by PCR, barcoded and sequenced using an Illumina Next-Seq 500 platform. Results: 25/34 patients had tumor metastasis. 135 non-silent mutations in 62 genes were detected in 27 tumor samples, while 7 patients’ samples had no mutation detected. CDH1, BRCA2 and SMAD4 gene mutations only occurred among metastasis patients. CDH1, BRCA2 and KRAS gene mutations are associated with a lower overall survival rate. Among them, 5 patients had a CDH1 mutation, including one splicing mutation, three frameshift mutations, one non-frameshift mutation and two non-synonymous mutations. All five patients had tumor metastasis, with the survival time less than 17 months, compared with all patients’ average overall survival of 22 month. Conclusions: Previous studies showed that mutation in CDH1 is linked to gastric cancer (GC) susceptibility and tumor invasion. Our results indicated that the mutation of CDH1 was also associated with the prognosis of gastric adenocarcinoma (P < .01) and was an independent factor (P < .05).

The clinical prognostic significance of lymphovascular invasion in gastric cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 428-428
Author(s):  
Hirohito Fujikawa ◽  
Takanobu Yamada ◽  
Keisuke Koumori ◽  
Hayato Watanabe ◽  
Kazuki Kano ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Prognostic Factor ◽  
Lymphatic Vessel ◽  
Lymphovascular Invasion ◽  
Venous Invasion ◽  
Nodal Metastasis ◽  
Node Metastasis ◽  
Significant Difference

428 Background: Lymphovascular invasion (LVI) of malignant tumor is regarded as an initial state of metastasis, including the lymph nodes, and therefore may be a prognostic factor in many malignancies. However, in gastric cancer, according to the current Japanese guidelines, LVI is not clinically useful information, except for in predicting the curability of endoscopic resection, and its clinicopathological characteristics and biological behavior remain unclear. The present study explored the histopathological significance of LVI in gastric cancer and clarified its correlation with the prognosis. Methods: From January 2000 to December 2013, a total of 2090 cases of gastric cancer undergoing radical gastrectomy were enrolled in this study. The correlation of LVI and other histopathological factors with the prognosis was evaluated. Lymphatic vessel invasion (ly) and venous invasion (v) were diagnosed followed the current Japanese classification. LVI positivity (LVIP) and LVI negativity (LVIN) were defined as the presence of lymphatic vessel and/or venous invasion and the absence of LVI, respectively. Results: LVIP was noted in 894 cases (42.8%). The age (p < 0.001), depth of tumor invasion (pT) (p < 0.001), lymph node metastasis (pN) (p < 0.001), and maximum tumor size (p < 0.001) were significantly correlated with the presence of LVI. A multivariate analysis showed that pT (p < 0.001), pN (p < 0.001), and LVI (p = 0.03) were independent risk factors for the prognosis of all patients. On analyzing the significance of every T factor and N factor for the overall survival of LVIP and LVIN cases, no significant difference was recognized in the prognosis among all pT1 patients and pT2-4 patients without nodal metastasis. However, in pT2-4 patients with nodal metastasis, a significant difference was revealed, and the 5-year overall survival rates in LVIP cases were lower than those in LVIN (60.9% [95% confidence interval: 56.3-65.3] vs. 76.7% [95% confidence interval 65.2-84.8], p = 0.005). Conclusions: LVI in gastric cancer is an independent prognostic factor, and its effect tends to be particularly strong in advanced cancer with lymph node metastasis. These patients may therefore require more effective adjuvant therapy.

scholarly journals CDH1 germline mutations in a Chinese cohort with hereditary diffuse gastric cancer

2021 ◽  
Author(s):  
Zhiwen Pan ◽  
Zhixuan Fu ◽  
Cong Luo ◽  
Yejiang Bao ◽  
Mingli Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Germline Mutations ◽  
Hereditary Diffuse Gastric Cancer ◽  
Chinese Patients ◽  
Diffuse Gastric Cancer ◽  
Chinese Cohort ◽  
Males And Females ◽  
Polymerase Chain ◽  
First Time ◽  
Index Cases

Abstract Purpose Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer (HDGC) and have been identified in multiple ethnicities. However, CDH1 germline mutations have seldom been documented in Chinese patients with HDGC, and their frequency remains unclear. Here, we aimed to examine the frequency of CDH1 germline mutations in Chinese patients with HDGC. In total, 285 patients who met the International Gastric Cancer Linkage Consortium 2015 testing criteria of HDGC for CDH1 germline mutations were recruited. Methods All 16 CDH1 exons, including neighboring intronic sequences, were amplified using polymerase chain reaction and screened using Sanger sequencing. Variants were analyzed using Mutation Surveyor V4.0, SIFT, and PolyPhen-2 software. Results Three nonsense and nine missense CDH1 germline mutations were identified in 21 of 285 index cases (7.4%). Two CDH1 germline mutations, N405Y (Asn405Tyr) and W409X (Trp409Ter) were identified as new variants. In addition, we found that up to 28.6% of CDH1 mutations in the 21 indicated patients identified as c.1775G > C (E551Q). The frequency of CDH1 mutations was 6.5% (7/108) in HDGC and 7.9% (14/177) in early onset diffuse gastric cancer (EODGC). The mutation detection rate of CDH1 in males and females was 6.7% (4/60) and 8.5% (10/117) in EODGC and 4.6% (3/65) and 9.3% (4/43) in HDGC, respectively. Conclusion These data reveal, for the first time, the type and frequency of CDH1 germline mutations in Chinese HDGC, and demonstrate that germline CDH1 mutations are a noteworthy contributor to the high frequency of HDGC in Chinese.

scholarly journals Hereditary Gastric Cancer: Review of Literature

2013 ◽  
Vol 13 (1) ◽  
pp. 71-74
Author(s):  
Jelena Pogodina ◽  
Genadijs Trofimovics ◽  
Edvins Miklasevics ◽  
Roberts Ribenieks
Keyword(s):  
Gastric Cancer ◽  
Future Research ◽  
Diffuse Gastric Cancer ◽  
High Morbidity ◽  
Review Of Literature ◽  
Cdh1 Gene ◽  
Preventative Measures ◽  
Cancer Review ◽  
Prophylactic Gastrectomy ◽  
Cdh1 Mutation

Summary Worldwide, gastric cancer is one of the most common forms of cancer, with a high morbidity and mortality. Both environmental and genetic factors have a role in the aetiology of gastric cancer. Familial clustering of gastric cancer is seen in 10-15% of cases, and approximately 3% of gastric cancer cases arise in the setting of hereditary diffuse gastric cancer ( HDGC). In families with HDGC, gastric cancer presents at relatively young age. Germline mutations in the CDH1 gene are the major cause of HDGC and are identified in approximately 25-40% of families which fulfill strict criteria. Prophylactic gastrectomy is the only option to prevent gastric cancer in individuals with a CDH1 mutation. However, in the majority of families with multiple cases of gastric cancer no germline genetic abnormality can be identified and therefore preventative measures are not available, except for general lifestyle advice. Future research should focus on identifying new genetic predisposing factors for all types of familial gastric cancer.

Impact of external-beam radiation therapy on outcomes among patients with resected gastric cancer: A multi-institutional analysis.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 84-84
Author(s):  
Aslam Ejaz ◽  
Gaya Spolverato ◽  
Yuhree Kim ◽  
Malcolm Hart Squires ◽  
Sharon M. Weber ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Tumor Size ◽  
Perioperative Therapy ◽  
Curative Intent ◽  
Factors Associated ◽  
Node Metastasis

84 Background: Use of perioperative chemotherapy (CTx) alone versus chemo-radiation therapy (cXRT) in the treatment of resectable gastric cancer remains varied. We sought to define the utilization and effect of CTx alone versus cXRT on patients having undergone curative-intent resection for gastric cancer. Methods: Using the multi-institutional U.S. Gastric Cancer Collaborative database, we identified 505 patients between 2000 and 2012 with gastric cancer who received perioperative therapy in addition to curative-intent resection. The impact of perioperative therapy on survival was analyzed by the use of propensity-score matching of clinicopathologic factors among patients who received CTx alone versus cXRT. Results: Median patient age was 62 years and the majority of patients were male (58%). Surgical resection involved either partial gastrectomy (54%) or total gastrectomy (46%). On pathology, median tumor size was 5.0 cm; most patients had a T3 (37%) or T4 (36%) lesion and lymph node metastasis (74%). Margin status was R0 in most patients (89%). 211 (42%) patients received perioperative CTx alone whereas the remaining 294 (58%) patients received 5-FU based cXRT. Factors associated with receipt of cXRT were younger age (OR 0.98), T3 tumors (OR 1.52), and lymph node metastasis (OR 2.03) (all P < .05). Recurrence occurred in 214 (39%) patients. At a median follow-up of 28 months, median overall survival (OS) was 33.4 months and 5-year survival was 36.7%. Factors associated with worse OS included tumor size (HR 1.1), T-stage (HR 1.5), and lymph node metastasis (HR 1.58) (all P<0.05). In contrast, receipt of cXRT was associated with improved long-term OS (CTx alone: 21 months vs. cXRT 45 months; p<0.001). In the propensity-matched multivariate model that adjusted for tumor size, T-stage, and nodal status, cXRT remained associated with an improved long-term disease-free (HR 0.43) and overall (HR 0.41) survival (both P<0.001). Conclusions: XRT was utilized in 58% of patients undergoing curative-intent resection for gastric cancer. Using propensity-matched analysis, cXRT was an independent factor associated with improved recurrence-free and overall survival.

scholarly journals CDH1 gene mutations do not contribute in hereditary diffuse gastric cancer in Poland

2010 ◽  
Vol 9 (4) ◽  
pp. 605-608 ◽  
Author(s):  
Anna Jakubowska ◽  
Małgorzata Ławniczak ◽  
Beata Wojnarska ◽  
Cezary Cybulski ◽  
Tomasz Huzarski ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gene Mutations ◽  
Hereditary Diffuse Gastric Cancer ◽  
Diffuse Gastric Cancer ◽  
Cdh1 Gene
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