Det rör sig om 2 helt nya upptäckter inom hudcancer.
Från UCSF,s hemsida
Evolution of Melanoma Reveals Opportunities for Intervention
Innovative CRISPR Study Recreates Genetic Steps Required for Benign Moles to Turn Malignant
In the first study, led by Bastian and UCSF cancer geneticist Hunter Shain, PhD, the researchers studied a unique dataset surgically removed melanoma tissue samples from 82 patients in which malignant tumors and the benign moles from which they had developed were preserved side-by-side. In a subset of patients, the researchers also obtained matched samples of metastatic tumors and the primary melanomas in the skin from which the metastatic colonies had derived.
By analyzing these 230 tissue samples, the researchers to compare molecular differences between benign growths, malignant melanomas, and metastatic colonies within the same patients.
The researchers sequenced tumor DNA to identify gene mutations arising at different stages of cancer evolution and also measured changes in RNA to connect these mutations to related changes in gene activity.
“This is the first study to profile both DNA and RNA from matching melanoma samples and precursor moles from the same patients,” Shain said.
The researchers found that as tumors progress, multiple independent gene mutations repeatedly tweak central molecular pathways controlling cell growth, tumor suppression and DNA regulation until enough mutations accumulate to break down cells’ natural protective mechanisms and trigger cancer.
Among other findings, the researchers found that moles consistently developed mutations in the SWI/SNF class of DNA regulatory genes as a key step in their transition to malignancy, suggesting this marker could be used clinically to identify dangerous moles in need of treatment.
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| Cancerous melanoma cells, shown with their cell bodies (green) and nuclei (blue). Credit: Sidi A. Bencherif, Thomas Ferrante / Wyss Institute at Harvard University |
In the second paper, led by UCSF melanoma geneticist Robert Judson, PhD, the researchers performed an innovative experiment to recreate and study the steps of melanoma evolution in a controlled laboratory setting. Using CRISPR-Cas9 gene editing, the scientists precisely inserted the sequence of mutations they had observed in clinical specimens into normal human skin cells in the lab.
This allowed the researchers to examine the specific biological effects of each step in melanomas’ evolution: for example, they were surprised to discover that mutations disrupting the central tumor suppressor gene CDKN2A did not simply unleash tumor growth, as had been predicted, but also caused affected cells to become highly mobile (and therefore more prone to invade and spread to other parts of the body) through activation of a transcription factor protein called BRN2.
In addition to identifying a key mechanism driving melanoma’s deadly ability to metastasize, the new research demonstrates a novel use for CRISPR gene-editing as a laboratory tool for studying melanoma.
“Previous studies have typically used cell lines derived from advanced-stage cancers, where there is so much going wrong at the genetic level that it’s hard to know what’s causing what,” Judson said. “Here we’re looking at otherwise healthy skin cells with specific mutations engineered in. It’s much clearer what each mutation does.”
The researchers hope this new tool and the discoveries it has already produced will significantly speed research into how to more rapidly diagnose and treat melanoma patients. In particular, they hope that their discoveries will be rapidly incorporated into clinical genetic tests that will allow physicians to quickly assess patients' risk of skin cancer and assign those at highest risk to early treatment.
“Because we haven’t had the tools to identify who is at high risk of metastasis, we have tended to treat everybody as if they were at high risk, exposing them to intense treatment and potential side effects,” Bastian said. “We anticipate that looking at genetic changes in melanoma samples here at UCSF will allow us to identify melanomas that have progressed to a dangerous state and deploy systemic treatments earlier, which will increase their effectiveness for our patients.”
Robert Judson känner vi sen tidigare. Bloggen har skrivit om hans forskning, bla här och här.
Ur pressmeddelandet från i morse:
Forskare vid UCSF-PHI Center of Excellence kartlägger den genetiska utvecklingen av metastatisk hudcancer
Genom att kombinera PHI:s HoloMonitor-teknik med den senaste tekniken inom genredigering har forskare vid University of California i San Francisco för första gången lyckas följa och kartlägga hur mutationer bryter ned det genetiska försvar som hindrar ofarliga leverfläckar från att utvecklas till metastatisk hudcancer.Forskningsresultaten, som utlovar förbättrad hudcancerbehandling genom att identifiera elakartade former tidigare, publicerades nyligen i två artiklar i den prestigefyllda och inflytelserika vetenskapliga tidskriften Cancer Cell.
"Det är vår roll och vision att tillhandahålla de nya vetenskapliga verktyg som den medicinska forskningen behöver för att åstadkomma banbrytande framsteg. Upptäckterna som forskarna vid USCF har gjort är ett utmärkt exempel på detta", säger Peter Egelberg, VD och grundare av PHI.
Länkar till artiklarna i Cancer Cell.
Bi-allelic Loss of CDKN2A Initiates Melanoma Invasion via BRN2 Activation
Volume 34, Issue 1, 9 July 2018, Pages 56-68.e9Genomic and Transcriptomic Analysis Reveals Incremental Disruption of Key Signaling Pathways during Melanoma Evolution
Volume 34, Issue 1, 9 July 2018, Pages 45-55.e4Min kommentar
Förutom ovanstående nyheter , som är av toppklass, verkar det som flödet av PHI relaterat som ex forskningsrapporter och publiceringar sätter fart igen.
Det i en "lugn" period som sommaren vanligtvis brukar vara.
Jag ser verkligen fram mot hösten (ur den synvinkeln).
Känns bra, känns riktigt bra.
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