NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 9 | JANUARY 2012 Nature Reviews Gastroenterology & Hepatology 9, 2 (2012); published online 13 December 2011; doi:10.1038/nrgastro.2011.239 RESEARCH HIGHLIGHTS The molecular identity of colorectal cancer (CRC) tissue at the single-cell level, in comparison with that of healthy colon tissue, has now been revealed by research published in Nature Biotechnology. “We wanted to develop a technique that could allow us to take a snapshot of the cell composition of both normal colon and colon cancer tissue,” say co-authors Dalerba, Kalisky & Sahoo. Using a microfluidic platform (enabling 9,216 COLORECTAL CANCER A single-cell snapshot of gene expression in healthy and cancerous colon tissue simultaneous real-time PCR reactions), hundreds of single cells from human colonic epithelia (healthy and both benign and malignant CRC samples) were analyzed to ‘dissect’ the different cell populations within the samples. Essentially, the transcriptional identities of multiple cell types were the same in normal and colon cancer tissue. Moreover, by monitoring the tumorigenesis of a single human CRC cell, the investigators have formally shown that the cellular diversity of cancer tissue can result from multilineage differentiation (that is, a single cell can recapitulate the diversity of a parent tumor) and not only by clonal evolution as a result of random genetic mutations. Finally, the researchers developed a novel prognostic two-gene scoring system—based on the expression of KRT20 with either CA1, MS4A12, CD177 or SLC26A3—that could predict patient outcome (disease- free survival), which compared favorably to traditional prognostic markers such as pathological grade. The group is now planning systematic screens for surface markers and/or therapeutic targets for colon cancer, and to adapt this system to screen other tissues. Katrina Ray Original article Dalerba, P. et al. Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nat. Biotechnol. doi:10.1038/nbt.2038 Presence of goblet cells in healthy colon tissue (left) and colon cancer tissue (right) by staining with anti-MUC2 antibodies. Courtesy of P . Dalerba, T. Kalisky & D. Sahoo. © 2011 Macmillan Publishers Limited. All rights reserved

Colorectal cancer: A single-cell snapshot of gene expression in healthy and cancerous colon tissue

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Page 1: Colorectal cancer: A single-cell snapshot of gene expression in healthy and cancerous colon tissue

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 9 | JANUARY 2012

Nature Reviews Gastroenterology & Hepatology 9, 2 (2012); published online 13 December 2011; doi:10.1038/nrgastro.2011.239

RESEARCH HIGHLIGHTS

The molecular identity of colorectal cancer (CRC) tissue at the single-cell level, in comparison with that of healthy colon tissue, has now been revealed by research published in Nature Biotechnology.

“We wanted to develop a technique that could allow us to take a snapshot of the cell composition of both normal colon and colon cancer tissue,” say co-authors Dalerba, Kalisky & Sahoo. Using a microfluidic platform (enabling 9,216

COLORECTAL CANCER

A single-cell snapshot of gene expression in healthy and cancerous colon tissue

simultaneous real-time PCR reactions), hundreds of single cells from human colonic epithelia (healthy and both benign and malignant CRC samples) were analyzed to ‘dissect’ the different cell populations within the samples.

Essentially, the transcriptional identities of multiple cell types were the same in normal and colon cancer tissue. Moreover, by monitoring the tumorigenesis of a single human CRC cell, the investigators have

formally shown that the cellular diversity of cancer tissue can result from multilineage differentiation (that is, a single cell can recapitulate the diversity of a parent tumor) and not only by clonal evolution as a result of random genetic mutations.

Finally, the researchers developed a novel prognostic two-gene scoring system—based on the expression of KRT20 with either CA1, MS4A12, CD177 or SLC26A3—that could predict patient outcome (disease-free survival), which compared favorably to traditional prognostic markers such as pathological grade.

The group is now planning systematic screens for surface markers and/or therapeutic targets for colon cancer, and to adapt this system to screen other tissues.

Katrina Ray

Original article Dalerba, P. et al. Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nat. Biotechnol. doi:10.1038/nbt.2038

Presence of goblet cells in healthy colon tissue (left) and colon cancer tissue (right) by staining with anti-MUC2 antibodies. Courtesy of P. Dalerba, T. Kalisky & D. Sahoo.