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2015 ; 21
(37
): 10510-27
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Challenges of deciphering gastric cancer heterogeneity
#MMPMID26457012
Hudler P
World J Gastroenterol
2015[Oct]; 21
(37
): 10510-27
PMID26457012
show ga
Gastric cancer is in decline in most developed countries; however, it still
accounts for a notable fraction of global mortality and morbidity related to
cancer. High-throughput methods are rapidly changing our view and understanding
of the molecular basis of gastric carcinogenesis. Today, it is widely accepted
that the molecular complexity and heterogeneity, both inter- and intra-tumour, of
gastric adenocarcinomas present significant obstacles in elucidating specific
biomarkers for early detection of the disease. Although genome-wide sequencing
and gene expression studies have revealed the intricate nature of the molecular
changes that occur in tumour landscapes, the collected data and results are
complex and sometimes contradictory. Several aberrant molecules have already been
tested in clinical trials, although their diagnostic and prognostic utilities
have not been confirmed thus far. The gold standard for the detection of sporadic
gastric cancer is still the gastric endoscopy, which is considered invasive. In
addition, genome-wide association studies have confirmed that genetic variations
are important contributors to increased cancer risk and could participate in the
initiation of malignant transformation. This hypothesis could in part explain the
late onset of sporadic gastric cancers. The elaborate interplay of polymorphic
low penetrance genes and lifestyle and environmental risk factors requires
additional research to decipher their relative impacts on tumorigenesis. The
purpose of this article is to present details of the molecular heterogeneity of
sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss
issues relevant to the translation of basic research data to clinically valuable
tools. The focus of this work is the identification of relevant molecular changes
that could be detected non-invasively.
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