TY - JOUR
T1 - The roles of chromatin-remodelers and epigenetic modifiers in kidney cancer
AU - Liao, Lili
AU - Testa, Joseph R.
AU - Yang, Haifeng
N1 - Publisher Copyright:
© 2015 Elsevier Inc..
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Clear cell renal cell carcinoma (ccRCC) is the major subtype of kidney cancer that is characterized by frequent inactivation of the von Hippel-Lindau (. VHL) gene in 80-90% of the tumors. Recent reports using massive parallel sequencing technologies have discovered additional cancer driver genes. PBRM1 was found to be mutated in about 40% of ccRCC tumors, whereas BAP1 and SETD2 were each mutated in about 10-15% of ccRCC tumors. JARID1C and UTX, two histone H3 demethylases, were also found to harbor mutations in ccRCC, albeit at lower rates. ccRCC tumors display a high degree of intra-tumoral heterogeneity, with some mutations present in all cancer cells (ubiquitous), whereas others are subclonal. The VHL mutations were always ubiquitous in the tumors; PBRM1 mutations were also ubiquitous but to a lesser extent. On the contrary, mutations in BAP1, SETD2, JARID1C, and UTX were all subclonal, meaning that they were present in a subset of cancer cells in a tumor. The prognostic value of PBRM1 mutations in ccRCC is still controversial, whereas BAP1 mutations were tightly linked to worse clinical outcomes in multiple studies. The molecular functions of these newly identified cancer driver genes are discussed, and they were known readers, writers, or erasers of histone marks on histone H2 and H3 tails that are very close to each other, suggesting that these factors might functionally interact and affect common pathways. The studies on these newly identified tumor suppressors will shed light on ccRCC tumorigenesis and development, and will likely lead to development of novel therapeutic interventions for ccRCC patients.
AB - Clear cell renal cell carcinoma (ccRCC) is the major subtype of kidney cancer that is characterized by frequent inactivation of the von Hippel-Lindau (. VHL) gene in 80-90% of the tumors. Recent reports using massive parallel sequencing technologies have discovered additional cancer driver genes. PBRM1 was found to be mutated in about 40% of ccRCC tumors, whereas BAP1 and SETD2 were each mutated in about 10-15% of ccRCC tumors. JARID1C and UTX, two histone H3 demethylases, were also found to harbor mutations in ccRCC, albeit at lower rates. ccRCC tumors display a high degree of intra-tumoral heterogeneity, with some mutations present in all cancer cells (ubiquitous), whereas others are subclonal. The VHL mutations were always ubiquitous in the tumors; PBRM1 mutations were also ubiquitous but to a lesser extent. On the contrary, mutations in BAP1, SETD2, JARID1C, and UTX were all subclonal, meaning that they were present in a subset of cancer cells in a tumor. The prognostic value of PBRM1 mutations in ccRCC is still controversial, whereas BAP1 mutations were tightly linked to worse clinical outcomes in multiple studies. The molecular functions of these newly identified cancer driver genes are discussed, and they were known readers, writers, or erasers of histone marks on histone H2 and H3 tails that are very close to each other, suggesting that these factors might functionally interact and affect common pathways. The studies on these newly identified tumor suppressors will shed light on ccRCC tumorigenesis and development, and will likely lead to development of novel therapeutic interventions for ccRCC patients.
KW - BAP1
KW - JARID1C/KDM5A
KW - PBRM1
KW - SETD2
KW - VHL
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UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000356644800005&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1016/j.cancergen.2015.02.008
DO - 10.1016/j.cancergen.2015.02.008
M3 - Review article
C2 - 25873528
SN - 2210-7762
VL - 208
SP - 206
EP - 214
JO - Cancer genetics
JF - Cancer genetics
IS - 5
ER -