scholarly journals Whole-Exome Sequencing Reveals Molecular Characterization of Early-Onset and Peritoneal Metastasis in Gastric Cancers

2021 ◽  
Author(s):  
Zhi-wei Zhou ◽  
Hai-bo Qiu ◽  
Xu-jun Wang ◽  
Wei Wang ◽  
Ting Wu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Molecular Characterization ◽  
Gastric Adenocarcinoma ◽  
Peritoneal Metastasis ◽  
Early Onset ◽  
Somatic Mutations ◽  
Cancer Center ◽  
Gastric Cancers ◽  
Younger Age ◽  
Cancer Aggressiveness

Abstract Background: Increasing numbers of Gastric cancer(GC) patients were diagnosed at younger age with aggressive behavior including early disease recurrence, more frequent peritoneal metastasis and poor overall survival. To investigate the driver genes and mechanisms of the early-onset and more aggressive nature of the GC.Methods: Gastric adenocarcinoma and matched germline samples were obtained from patients in Sun Yat-sen University Cancer Center between 2007 and 2013. Exome sequencing were performed for 198 pairs of primary gastric adenocarcinoma fresh tissue and blood samples from young or elder patients. Besides, matched tumor / blood exome sequencing was performed in 80 patients with peritoneal seeding and 51 patients without. Then bioinformatics analysis was performed to find genomic variants and their clinical meanings.Results: Early-onset gastric cancers (EOGCs) have fewer somatic mutations but some deleterious germline variates in FAT genes, patients carried none, one, two, three of the 4 Single nucleotide polymorphisms (SNPs), the mean ages of diagnosis are 60, 50, 40 and 35 respectively. Somatic mutations in CDH1, TGFBR1 and CTNNB1 are related to early-onset cancers. These variants are all linked to WNT pathways. Somatic mutations in genes involved in cancer aggressiveness like MAP2K7, CDH1 and RhoA are related to cancer progression and metastasis. Patients carrying RhoA, ITGAV, TGFBR1, CDH1, CTNNB1, MYO9B, VAV1, SALL1, CDX4 somatic mutations or simultaneously carrying three FAT germline SNPs have been diagnosed at younger age than those have only TP53 mutations.Conclusions: The molecular characterization gives us a novel insight into the carcinogenesis and tumor progression mechanisms and may provide a guide to developing novel targeted therapy in GC.

scholarly journals Whole-exome sequencing to identify somatic mutations in peritoneal metastatic gastric adenocarcinoma: A preliminary study

Oncotarget ◽  
2016 ◽  
Vol 7 (28) ◽  
pp. 43894-43906 ◽  
Author(s):  
Hao Liu ◽  
Fengping Li ◽  
Yu Zhu ◽  
Tingting Li ◽  
Haipeng Huang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Gastric Adenocarcinoma ◽  
Somatic Mutations ◽  
Whole Exome ◽  
Preliminary Study

scholarly journals Outcomes of Patients with Early Onset Colorectal Cancer Treated in a UK Specialist Cancer Center

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1558 ◽  
Author(s):  
Georgiou ◽  
Khakoo ◽  
Edwards ◽  
Minchom ◽  
Kouvelakis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Multimodality Treatment ◽  
Outcome Data ◽  
Stage Ii ◽  
Cancer Center ◽  
Curative Surgery ◽  
Disease Biology ◽  
Younger Age ◽  
Early Onset Colorectal Cancer

The incidence of early onset colorectal cancer (EOCRC) is rapidly increasing, but there remains paucity of outcome data for young CRC patients. We reviewed the characteristics and outcomes of 241 adults, age <50, who were diagnosed with EOCRC between January 2009 and December 2014. Median age was 42, 56% were male, and 7% had hereditary etiology. Seventy percent had left-sided primaries. At diagnosis, 11%, 50%, and 39% had stage II, III, and IV CRC. Of the patients with stage II and III CRC who underwent curative surgery, 60% and 88% had adjuvant chemotherapy, with 5-year relapse free survival of 82% and 74% respectively. Of the 123 patients with metastatic (m) EOCRC, 93%, 63%, 33%, and 12% had 1st, 2nd, 3rd, and 4th line systemic anticancer therapy (SACT) respectively. For first line SACT, 99% had doublet chemotherapy, with bevacizumab or an anti-EGFR antibody in 57%. Median overall survival (mOS) of mEOCRC patients was 20.1 months (95% C.I: 15.9–23.2). Younger age and signet cells were associated with shorter mOS, whereas more lines of SACT and curative metastasectomy with longer mOS. Metastatic EOCRC patients had poorer outcomes than expected, despite optimal multimodality treatment. This suggests an aggressive disease biology that warrants further research and therapy development.

scholarly journals Recurrent Somatic Mutations in Human Gastric Cancers Identified by Whole Exome Sequencing

2012 ◽  
Vol 143 (5) ◽  
pp. 1385-1387 ◽  
Author(s):  
Takahiro Shimizu ◽  
Hiroyuki Marusawa ◽  
Tsutomu Chiba
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Somatic Mutations ◽  
Gastric Cancers ◽  
Whole Exome

Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes

2012 ◽  
Vol 44 (5) ◽  
pp. 570-574 ◽  
Author(s):  
Zhi Jiang Zang ◽  
Ioana Cutcutache ◽  
Song Ling Poon ◽  
Shen Li Zhang ◽  
John R McPherson ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Exome Sequencing ◽  
Gastric Adenocarcinoma ◽  
Chromatin Remodeling ◽  
Somatic Mutations

Utility and implications of exome sequencing in early‐onset Parkinson's disease

2018 ◽  
Vol 34 (1) ◽  
pp. 133-137 ◽  
Author(s):  
Joanne Trinh ◽  
Katja Lohmann ◽  
Hauke Baumann ◽  
Alexander Balck ◽  
Max Borsche ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Exome Sequencing ◽  
Early Onset ◽  
Early Onset Parkinson’S Disease

scholarly journals High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer

2021 ◽  
pp. jmedgenet-2020-107347
Author(s):  
D Gareth Evans ◽  
Elke Maria van Veen ◽  
Helen J Byers ◽  
Sarah J Evans ◽  
George J Burghel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Onset ◽  
Ductal Carcinoma ◽  
Cancer Genes ◽  
Early Onset Breast Cancer ◽  
Younger Women ◽  
Pathogenic Variants ◽  
Younger Age ◽  
Predisposition Genes

BackgroundWhile the likelihood of identifying constitutional breast cancer-associated BRCA1, BRCA2 and TP53 pathogenic variants (PVs) increases with earlier diagnosis age, little is known about the correlation with age at diagnosis in other predisposition genes. Here, we assessed the contribution of known breast cancer-associated genes to very early onset disease.MethodsSequencing of BRCA1, BRCA2, TP53 and CHEK2 c.1100delC was undertaken in women with breast cancer diagnosed ≤30 years. Those testing negative were screened for PVs in a minimum of eight additional breast cancer-associated genes. Rates of PVs were compared with cases ≤30 years from the Prospective study of Outcomes in Sporadic vs Hereditary breast cancer (POSH) study.ResultsTesting 379 women with breast cancer aged ≤30 years identified 75 PVs (19.7%) in BRCA1, 35 (9.2%) in BRCA2, 22 (5.8%) in TP53 and 2 (0.5%) CHEK2 c.1100delC. Extended screening of 184 PV negative women only identified eight additional actionable PVs. BRCA1/2 PVs were more common in women aged 26–30 years than in younger women (p=0.0083) although the younger age group had rates more similar to those in the POSH cohort. Out of 26 women with ductal carcinoma in situ (DCIS) alone, most were high-grade and 11/26 (42.3%) had a PV (TP53=6, BRCA2=2, BRCA1=2, PALB2=1). This PV yield is similar to the 61 (48.8%) BRCA1/2 PVs identified in 125 women with triple-negative breast cancer. The POSH cohort specifically excluded pure DCIS which may explain lower TP53 PV rates in this group (1.7%).ConclusionThe rates of BRCA1, BRCA2 and TP53 PVs are high in very early onset breast cancer, with limited benefit from testing of additional breast cancer-associated genes.

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