Genome regulation, cell circuitry, and epigenomics

Gene expression signatures indicate loss of function by master regulators of the genome

Corie Lok — Fri, 07 Apr 2023 14:11:15 +0000

Gene expression signatures indicate loss of function by master regulators of the genome

By Corie Lok April 7, 2023

Gene expression signatures indicate loss of function by master regulators of the genome

Study findings may help researchers predict which patients with tumors may benefit from certain drug candidates.

By Rob Levy, Dana-Farber Cancer Institute Communications

April 7, 2023

Credit: ӳ��ý Communications

Second only to the notorious TP53 gene, the genes for assemblages known as mSWI/SNF protein complexes are the most frequently mutated entities in cancer cells. Made up of 10-15 subunits, the complexes are built from the activity of 29 individual genes. The complexes play a key role in modifying chromatin – the twists of DNA and proteins that constitute chromosomes – so that genes become more or less active, switched on or switched off. Mutated forms of the genes responsible for mSWI/SNF complexes are found in more than 20 percent of human cancers. In some cases, it is the absence or alteration of one or more of the complexes' subunits that causes cancer.

In a new study, scientists at Dana-Farber Cancer Institute and the ӳ��ý of MIT and Harvard, including Cigall Kadoch, an institute member at ӳ��ý and an associate professor at Dana-Farber, used CRISPR-Cas9 technology to systematically stifle the roughly 29 genes associated with mSWI/SNF complexes, individually and in informative combinations in the context of a cancer cell. They tracked how each shutdown affected the structure and make-up of the complexes. The researchers then used the data to predict and identify, across thousands of human cancer gene expression profiles, which tumors harbor a mutation that results in a loss of mSWI/SNF function or which have gene expression patterns that mirror mSWI/SNF mutations. The findings may help doctors determine whether changes in this complex are playing important roles in a patient's cancer. Knowing these signatures, researchers aim to be better able to predict which tumors are likely to respond to the growing array of drug agents that target mSWI/SNF complexes in patients with cancer.

Funding:

This work was supported in part by awards from the National Institutes of Health; the American Cancer Society; the Pew-Stewart Scholars in Cancer Research; and the Klarman Cell Observatory.

Paper cited:

Otto JE, Ursu O et al. Structural and functional properties of mSWI/SNF chromatin remodeling complexes revealed through single-cell perturbation screens. Molecular Cell. Online April 6, 2023. DOI: 10.1016/j.molcel.2023.03.013

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Genome regulation, cell circuitry, and epigenomics

Cancer

New DNA sequencing technique preserves cells’ locations within tissues

tulrich@broadinstitute.org — Wed, 15 Dec 2021 16:05:12 +0000

Gene expression signatures indicate loss of function by master regulators of the genome

By Corie Lok April 7, 2023

Gene expression signatures indicate loss of function by master regulators of the genome

Study findings may help researchers predict which patients with tumors may benefit from certain drug candidates.

By Rob Levy, Dana-Farber Cancer Institute Communications

April 7, 2023

Credit: ӳ��ý Communications

Funding:

This work was supported in part by awards from the National Institutes of Health; the American Cancer Society; the Pew-Stewart Scholars in Cancer Research; and the Klarman Cell Observatory.

Paper cited:

Tags:

Genome regulation, cell circuitry, and epigenomics

Cancer

Tumors hide from the immune system with help from this protein

Corie Lok — Wed, 05 May 2021 13:39:21 +0000

Gene expression signatures indicate loss of function by master regulators of the genome

By Corie Lok April 7, 2023

Gene expression signatures indicate loss of function by master regulators of the genome

Study findings may help researchers predict which patients with tumors may benefit from certain drug candidates.

By Rob Levy, Dana-Farber Cancer Institute Communications

April 7, 2023

Credit: ӳ��ý Communications

Funding:

This work was supported in part by awards from the National Institutes of Health; the American Cancer Society; the Pew-Stewart Scholars in Cancer Research; and the Klarman Cell Observatory.

Paper cited:

Tags:

Genome regulation, cell circuitry, and epigenomics

Cancer

#WhyIScience Q&A: A computational and molecular biologist helps inspire the next generation of scientists

Eilidh Gilbert — Mon, 29 Mar 2021 13:15:31 +0000

Gene expression signatures indicate loss of function by master regulators of the genome

By Corie Lok April 7, 2023

Gene expression signatures indicate loss of function by master regulators of the genome

Study findings may help researchers predict which patients with tumors may benefit from certain drug candidates.

By Rob Levy, Dana-Farber Cancer Institute Communications

April 7, 2023

Credit: ӳ��ý Communications

Funding:

This work was supported in part by awards from the National Institutes of Health; the American Cancer Society; the Pew-Stewart Scholars in Cancer Research; and the Klarman Cell Observatory.

Paper cited:

Tags:

Genome regulation, cell circuitry, and epigenomics

Cancer

New immunotherapy target discovered for malignant brain tumors

tulrich@broadinstitute.org — Tue, 16 Feb 2021 14:00:00 +0000

Gene expression signatures indicate loss of function by master regulators of the genome

By Corie Lok April 7, 2023

Gene expression signatures indicate loss of function by master regulators of the genome

Study findings may help researchers predict which patients with tumors may benefit from certain drug candidates.

By Rob Levy, Dana-Farber Cancer Institute Communications

April 7, 2023

Credit: ӳ��ý Communications

Funding:

This work was supported in part by awards from the National Institutes of Health; the American Cancer Society; the Pew-Stewart Scholars in Cancer Research; and the Klarman Cell Observatory.

Paper cited:

Tags:

Genome regulation, cell circuitry, and epigenomics

Cancer

Epigenomic map reveals circuitry of 30,000 human disease regions

tulrich@broadinstitute.org — Mon, 08 Feb 2021 16:56:59 +0000

Gene expression signatures indicate loss of function by master regulators of the genome

By Corie Lok April 7, 2023

Gene expression signatures indicate loss of function by master regulators of the genome

Study findings may help researchers predict which patients with tumors may benefit from certain drug candidates.

By Rob Levy, Dana-Farber Cancer Institute Communications

April 7, 2023

Credit: ӳ��ý Communications

Funding:

This work was supported in part by awards from the National Institutes of Health; the American Cancer Society; the Pew-Stewart Scholars in Cancer Research; and the Klarman Cell Observatory.

Paper cited:

Tags:

Genome regulation, cell circuitry, and epigenomics

Cancer

Study hints at why an aggressive form of brain cancer is hard to treat

Abbey Bigler — Thu, 18 Jul 2019 15:00:00 +0000

Gene expression signatures indicate loss of function by master regulators of the genome

By Corie Lok April 7, 2023

Gene expression signatures indicate loss of function by master regulators of the genome

Study findings may help researchers predict which patients with tumors may benefit from certain drug candidates.

By Rob Levy, Dana-Farber Cancer Institute Communications

April 7, 2023

Credit: ӳ��ý Communications

Funding:

This work was supported in part by awards from the National Institutes of Health; the American Cancer Society; the Pew-Stewart Scholars in Cancer Research; and the Klarman Cell Observatory.

Paper cited:

Tags:

Genome regulation, cell circuitry, and epigenomics

Cancer

Researchers map new cellular atlas of acute myeloid leukemia

tulrich@broadinstitute.org — Thu, 28 Feb 2019 16:05:46 +0000

Gene expression signatures indicate loss of function by master regulators of the genome

By Corie Lok April 7, 2023

Gene expression signatures indicate loss of function by master regulators of the genome

Study findings may help researchers predict which patients with tumors may benefit from certain drug candidates.

By Rob Levy, Dana-Farber Cancer Institute Communications

April 7, 2023

Credit: ӳ��ý Communications

Funding:

This work was supported in part by awards from the National Institutes of Health; the American Cancer Society; the Pew-Stewart Scholars in Cancer Research; and the Klarman Cell Observatory.

Paper cited:

Tags:

Genome regulation, cell circuitry, and epigenomics

Cancer

New type of map connects the dots in cellular reprogramming

tulrich@broadinstitute.org — Thu, 31 Jan 2019 16:01:46 +0000

Gene expression signatures indicate loss of function by master regulators of the genome

By Corie Lok April 7, 2023

Gene expression signatures indicate loss of function by master regulators of the genome

Study findings may help researchers predict which patients with tumors may benefit from certain drug candidates.

By Rob Levy, Dana-Farber Cancer Institute Communications

April 7, 2023

Credit: ӳ��ý Communications

Funding:

This work was supported in part by awards from the National Institutes of Health; the American Cancer Society; the Pew-Stewart Scholars in Cancer Research; and the Klarman Cell Observatory.

Paper cited:

Tags:

Genome regulation, cell circuitry, and epigenomics

Cancer

Crosstalk between immune and intestinal stem cells may help maintain a healthy gut

tulrich@broadinstitute.org — Thu, 01 Nov 2018 15:30:02 +0000

Gene expression signatures indicate loss of function by master regulators of the genome

By Corie Lok April 7, 2023

Gene expression signatures indicate loss of function by master regulators of the genome

Study findings may help researchers predict which patients with tumors may benefit from certain drug candidates.

By Rob Levy, Dana-Farber Cancer Institute Communications

April 7, 2023

Credit: ӳ��ý Communications

Funding:

This work was supported in part by awards from the National Institutes of Health; the American Cancer Society; the Pew-Stewart Scholars in Cancer Research; and the Klarman Cell Observatory.

Paper cited:

Tags:

Genome regulation, cell circuitry, and epigenomics

Cancer