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allied
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CARDIOLOGY AND CARDIOVASCULAR MEDICINE
STEM CELLS AND REGENERATIVE MEDICINE
&
International Conference on
International Conference on
J u n e 1 8 - 1 9 , 2 0 1 8 | O s a k a , J a p a n
Biomedical Research
|
Volume 29
Page 16
Note:
Joint Event on
S
tem cell populations of columnar epithelia collectively resist cloning
in their immature states. By modifying the culture technique for
human intestinal stem cells, we have cultured the stem cells from
precancerous lesion known as Barretts esophagus which is intestinal
metaplasia, emerged from a squamocolumnar junction and would
eventually evolve to esophageal adenocarcinoma. Here we report the
isolation and propagation of distinct, patient-matched stem cells of
Barrett’s, gastric and esophageal epithelia that yield divergent tumor
types following
in vitro
transformation and xenografting. Exome-seq
revealed a broadmutational spectrumunique to Barrett’s stemcells that
likely reflect the risk for oncogenesis. Remarkably, 25% of cases show
no cancer-related genomic changes, suggesting that Barrett’s initiates
without driver mutations. Most cases, however, sustain patterns of
deletionsalmost identical toadenocarcinoma. Notably, thosesuspected
of low-grade dysplasia have p53 mutations or undergo amplifications
of proto-oncogenes and receptor tyrosine kinases, implicating these
events in lethal transitions. Our findings suggest paths for the initiation
and progression of Barrett’s esophagus and define a discrete stem cell
underlying its regenerative growth whose eradication could prevent
esophageal adenocarcinoma.
Figure1: A strategy for the stem cell culture of Barrett’s, esophagus and gastric stem cells
Related Publication
Yusuke Yamamoto, Xia Wang, et al., (2016) Mutational spectrum of
Barrett’s stem cells suggests paths to initiation of a precancerous
lesion. Nature Communications. 7: 10380
Biography
Yusuke Yamamoto has completed his PhD in
Molecular Physiology from Waseda University in
2008 and postdoctoral studies under Prof. Frank
McKeon and A/Prof. Wa Xian at Genome Institute
of Singapore. He has been interested in how adult
stem cells maintain their stemness throughout
the lifespan as well as identifying cell-of-origin in
esophageal adenocarcinomas and high grade se-
rous ovarian carcinoma, which are most aggres-
sive type of cancers with poor prognosis. He has
published more than 40 papers in reputed jour-
nals, including Nature and Cell.
yuyamamo@ncc.go.jpCLONING BARRETT’S
STEM CELLS SUGGESTS
PATHS TO INITIATION OF A
PRECANCEROUS LESION
Yusuke Yamamoto
National Cancer Center Research Institute
Japan
Yusuke Yamamoto, Biomed Res 2018, Volume 29 | DOI: 10.4066/biomedicalresearch-C2-004