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Center for Cancer Research
View the latest research highlights and featured publications from the Center for Cancer Research.
The unique strengths of the Center for Cancer Research (CCR) are the exceptional quality of its faculty and the ways in which the CCR's basic scientists collaborate with Mass General’s leading oncologists, surgeons, radiologists, pathologists, and other health care professionals to advance the frontiers of cancer medicine.
Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.
In this April 2018 paper published in Science, a group of researchers from the MGH and the Broad Institute used single-cell RNA-seq to define the cellular context of diffuse midline gliomas with histone H3 lysine27-to-methionine (H3K27M) mutations. These uniformly fatal malignancies arise primarily in the midline of the central nervous system of young children, suggesting a particular cell type present at this location and developmental stage is susceptible to transformation by H3K27M. By sequencing the RNA from 3321 single cells from 6 tumors, the authors found that H3K27M tumors largely consist of cells that resemble oligodendrocyte precursor cells (OPC) and drive the growth of the tumor, whereas more differentiated cells were in the minority and lacked proliferative potential. The authors suggest that targeting the OPC marker PDGFRA or triggering cells to differentiate might allow therapeutic intervention in these as yet incurable malignancies. For more information, click here.
This work was led by first authors Mariella Filbin (pictured), Itay Tirosh and Volker Hovestadt (pictured). It was made possible by a close collaboration between the laboratory of Mario Suva’s (pictured), Brad Bernstein and Aviv Regev.
A mitosis-specific and R loop-driven ATR pathway promotes faithful chromosome segregation.
ATR is a master kinase that regulates the DNA damage response, and it is particularly important during DNA replication to keep the genome stable. Although loss of ATR loss was known to cause problems in mitosis, these effects were thought to be indirect. In a January 2018 paper published in Science, Lilian Kabeche and colleagues in Lee Zou’s lab (pictured) report their discovery of a surprising function of ATR in mitosis. In early mitosis ATR is localized to and activated at centromeres. The activation of ATR at centromeres requires R loops, a transcription intermediate containing DNA:RNA hybrids and single-stranded DNA. Active ATR at centromeres promotes accurate segregation of whole chromosomes by stimulating the Aurora B kinase, ensuring that microtubules are attached to chromosomes properly. This study uncovers the first R loop-driven signaling cascade on chromosomes, and a new ATR pathway that specifically operates in mitosis, revealing an unexpected dimension of cell cycle regulation.
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