TY - JOUR
T1 - Liquid biopsy reveals collateral tissue damage in cancer
AU - Lubotzky, Asael
AU - Zemmour, Hai
AU - Neiman, Daniel
AU - Gotkine, Marc
AU - Loyfer, Netanel
AU - Piyanzin, Sheina
AU - Ochana, Bracha Lea
AU - Lehmann-Werman, Roni
AU - Cohen, Daniel
AU - Moss, Joshua
AU - Magenheim, Judith
AU - Loftus, Maureen F.
AU - Brais, Lauren
AU - Ng, Kimmie
AU - Mostoslavsky, Raul
AU - Wolpin, Brian M.
AU - Zick, Aviad
AU - Maoz, Myriam
AU - Grinshpun, Albert
AU - Kustanovich, Anatoli
AU - Makranz, Chen
AU - Cohen, Jonathan E.
AU - Peretz, Tamar
AU - Hubert, Ayala
AU - Temper, Mark
AU - Salah, Azzam
AU - Avniel-Polak, Shani
AU - Grozinsky-Glasberg, Simona
AU - Spalding, Kirsty L.
AU - Rokach, Ariel
AU - Kaplan, Tommy
AU - Glaser, Benjamin
AU - Shemer, Ruth
AU - Dor, Yuval
N1 - Publisher Copyright:
© 2022, Lubotzky et al.
PY - 2022/1/25
Y1 - 2022/1/25
N2 - Cancer inflicts damage to surrounding normal tissues, which can culminate in fatal organ failure. Here, we demonstrate that cell death in organs affected by cancer can be detected by tissuespecific methylation patterns of circulating cell-free DNA (cfDNA). We detected elevated levels of hepatocyte-derived cfDNA in the plasma of patients with liver metastases originating from different primary tumors, compared with cancer patients without liver metastases. In addition, patients with localized pancreatic or colon cancer showed elevated hepatocyte cfDNA, suggesting liver damage inflicted by micrometastatic disease, by primary pancreatic tumor pressing the bile duct, or by a systemic response to the primary tumor. We also identified elevated neuron-, oligodendrocyte-, and astrocyte-derived cfDNA in a subpopulation of patients with brain metastases compared with cancer patients without brain metastasis. Cell type-specific cfDNA methylation markers enable the identification of collateral tissue damage in cancer, revealing the presence of metastases in specific locations and potentially assisting in early cancer detection.
AB - Cancer inflicts damage to surrounding normal tissues, which can culminate in fatal organ failure. Here, we demonstrate that cell death in organs affected by cancer can be detected by tissuespecific methylation patterns of circulating cell-free DNA (cfDNA). We detected elevated levels of hepatocyte-derived cfDNA in the plasma of patients with liver metastases originating from different primary tumors, compared with cancer patients without liver metastases. In addition, patients with localized pancreatic or colon cancer showed elevated hepatocyte cfDNA, suggesting liver damage inflicted by micrometastatic disease, by primary pancreatic tumor pressing the bile duct, or by a systemic response to the primary tumor. We also identified elevated neuron-, oligodendrocyte-, and astrocyte-derived cfDNA in a subpopulation of patients with brain metastases compared with cancer patients without brain metastasis. Cell type-specific cfDNA methylation markers enable the identification of collateral tissue damage in cancer, revealing the presence of metastases in specific locations and potentially assisting in early cancer detection.
UR - http://www.scopus.com/inward/record.url?scp=85123904525&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.153559
DO - 10.1172/jci.insight.153559
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C2 - 35076021
AN - SCOPUS:85123904525
SN - 2379-3708
VL - 7
JO - JCI insight
JF - JCI insight
IS - 2
M1 - e153559
ER -
