Gene/Protein
Disease
Symptom
Drug
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Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
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Query: UMLS:C0033036 (
APC
)
10,214
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Early gastric cancers (EGCs) precede advanced gastric cancers (AGCs), with a favourable prognosis compared to AGC. To understand the progression mechanism of
EGC
to AGC, it is required to disclose
EGC
and AGC genomes in mutational and evolutionary perspectives. We performed whole-exome sequencing and copy number profiling of nine microsatellite (MS)-unstable (MSI-H) (five EGCs and four AGCs) and eight MS-stable (MSS) gastric cancers (four EGCs and four AGCs). In the cancers, we observed well-known driver mutations (TP53,
APC
, PIK3CA, ARID1A, and KRAS) that were enriched in cancer-related pathways, including chromatin remodelling and tyrosine kinase activity. The MSI-H genomes harboured ten times more mutations, but were largely depleted of copy number alterations (CNAs) compared to the MSS cancers. Interestingly,
EGC
genomes showed a comparable level of mutations to AGC in terms of the number, sequence composition, and functional consequences (potential driver mutations and affected pathways) of mutations. Furthermore, the CNAs between
EGC
and AGC genomes were not significantly different in either MSI-H and MSS. Evolutionary analyses using somatic mutations and MSI as molecular clocks further identified that
EGC
genomes were as old as AGC genomes in both MSS and MSI-H cancers. Our results suggest that the genetic makeup for gastric cancer may already be achieved in
EGC
genomes and that the time required for transition to AGC may be relatively short. Also, the data suggest a possibility that the mutational profiles obtained from early biopsies may be useful in the clinical settings for the molecular diagnosis and therapeutics of gastric cancer patients.
...
PMID:The mutational burdens and evolutionary ages of early gastric cancers are comparable to those of advanced gastric cancers. 2504 71
This study evaluated the possibility of endoscopic submucosal dissection (ESD) for early gastric cancer with papillary adenocarcinoma (EGC-PAC).
PAC
, an uncommon pathologic type of stomach cancer, is classified into differentiated-type histology. However, aggressive features, including a high rate of submucosal invasion, lymphovascular invasion (LVI), and lymph node metastasis (LNM), have been reported in studies with surgical specimens. Treatment outcomes of ESD for
EGC
-
PAC
have not been precisely demonstrated. Core databases were sought for the following inclusion criteria: studies of endoscopic resection or surgery of
EGC
-
PAC
presenting the following therapeutic indicators; en bloc resection, complete resection, curative resection, recurrence, complications associated with procedures, LVI, or LNM that enabled an analysis of ESD possibility. Overall, 15 studies were included for systematic review. Frequent submucosal invasion and high LVI were noted in
EGC
-
PAC
. However,
PAC
was not significantly associated with LNM. Pooled en bloc resection, complete resection, and curative resection rates were 89.7% (95% confidence interval: 55.3%-98.4%), 85.3% (67.7%-94.2%), and 67% (43%-84.5%), respectively. No LNM was observed if
EGC
-
PAC
satisfied the curative resection criteria. ESD seems technically feasible, although a high LVI rate results in a lower rate of curative resection.
...
PMID:Endoscopic Submucosal Dissection of Papillary Gastric Adenocarcinoma; Systematic Review. 3242 68