Science

Ask me anything at PLOS Science Wednesday on May 18

PLOS Science Wednesday is a weekly science communication series featuring live, direct chats with PLOS authors on redditscience (/r/science), the popular online gathering place for researchers, students and others interested in science which has over 8 million registered members. The series provides a forum for PLOS authors to communicate their work and interact directly with fellow researchers and the public.

You can find the complete schedule here.

And on May 18th it’s my turn to answer anything together with my colleague James Brenton.

And when I say ‘anything’ I mean ‘anything about cancer evolution’.

Florian

Career, Science

Open positions – cancer evolution and networks

I have three open positions in my lab:

  1. A PhD student position for “Single-cell analysis of cancer evolution” http://www.jobs.cam.ac.uk/job/10282/
  2. A postdoc position for “Evolutionary biology in cancer”. This position is ideal for somebody trained in evolutionary biology in model systems to make the transition to biomedical applications in cancer.
  3. And finally a postdoc position broadly advertised as “Computational cancer genomics” but actually having a strong network focus. http://www.jobs.cam.ac.uk/job/10265/

More info here http://www.markowetzlab.org/positions.php

Any questions, just contact me directly.

Florian

Science

Inferring tumor evolution from single-cell genomes

Series on Tumor Evolution

Everything is better if you do it with a Nested Effects Model – even inferring tumor evolution.

Let me introduce to you Oncogenetic Nested Effects Models, or for short OncoNEMs, which we just published in the new Single Cell collection of Genome Biology (see here). They exploit the fact that tumors accumulate mutations while they evolve, which leads to (noisy) subset relations between clones – exactly the type of pattern NEMs were made for.

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Creativity

Lit with a ghoulish inner light — Three Oncologists for Halloween

The scariest picture I have seen this Halloween (or maybe even ever) is Ken Currie’s eerie portrait Three Oncologists:

The Three Oncologists are Professor RJ Steele, Professor Sir Alfred Cuschieri and Professor Sir David P Lane of the Department of Surgery and Molecular Oncology, Ninewells Hospital, Dundee. *

In the Guardian Kathleen Jamie writes:

It’s a portrait, but far from flattering. (…) The three men are lit with a ghoulish inner light; they seem to be haunting the threshold between life and death. (…)

Furthermore, they hold their tools or means: Steele raises his gloved and bloodstained hands, Cuschieri holds a surgeon’s implement, Lane carries a paper. Whose sentence is written there?

As we grow more able to say the word “cancer” out loud and more of us survive it, thanks in no small part to our surgeons and physicians, this painting will become a historical record of an emotional state, as well as honouring three esteemed medics.

But it will still send a shiver down the spine.

It sure will.

Florian

Science

Inferring tumour evolution 7 – the roots of metastasis

Series on Tumour Evolution

What makes a cancer deadly is not necessarily the growth at the location where it started (the primary tumour) but its spread through the body to other organs and tissues (called metastasis). Better understanding the metastatic process is one of main reasons we are interested in inferring cancer evolution.

Today I would like to summarize and discuss two recent papers on cancer phylogenetics and metastasis. The first paper is the comprehensive review by Naxerova and Jain in Nature Reviews Clinical Oncology titled “Using tumour phylogenetics to identify the roots of metastasis in humans.” The second paper is an Opinion paper by Hong, Shpak and Townsend in Cancer Research  titled “Inferring the origin of metastases from cancer phylogenies.”

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Science

Inferring tumour evolution – clones, again

Series on Tumor Evolution
How do you know the leaders in your field? Because they get invited by
Nature Medicine and Nature Biotechnology to a fancy place owned by the Volkswagen Foundation and write a report about it. For example, this one in the latest issue of Nature Medicine titled Toward understanding and exploiting tumor heterogeneity.

What did they discuss? Lots of things. But I got stuck already in the very first topic:

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Science

A unifying theory of cancer evolution: genomes in context

Finally a review article on cancer evolution that I really enjoyed. Maybe because it’s not a Review but an Opinion piece: “Evolutionary dynamics of carcinogenesis and why targeted therapy does not work” by Gillies, Verduzco and Gatenby (GVG for short).

Extra brownie points for a provocative title.

The first publication on tumor heterogeneity

First of all, GVG extended my knowledge of the history of tumor heterogeneity by citing a paper from 1930:

Ö. Winge, Zytologische Untersuchungen über die Natur maligner Tumoren, Zeitschrift für Zellforschung und Mikroskopische Anatomie, 6. JUNI 1930, Volume 10, Issue 4, pp 683-735,

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Science

Evolution in cancer: Yes! Darwin: No?

Series on Tumor Evolution

ResearchBlogging.org
Evolution is a fancy word for gradual change. In this general sense, all kinds of things evolve. The universe evolves, societies evolve, finches evolve.

The mechanisms and principles of these three evolutions are all different. For example, the finches change by Darwinian evolution, which is one particular type of evolution based on natural selection: There is diversity in traits between individuals in a population; because of their traits some individuals have more offspring than others; the traits are heritable and can be passed on to offspring. Over time the favorable traits will become dominant in the population – and with them the genotypes underlying them.

This is how it works for finches. How about cancer? Is that developing by Darwinian evolution too? Not so fast, say Sidow and Spies:

The forced application of terms and concepts from organismal population genetics can distract from the fundamental simplicity of cancer evolution,

write Sidow and Spies in their review ‘Concepts in solid tumor evolution‘ (TiG 2015) and they plan to set the record straight.

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Creativity, Science

Healing Art of Pathology

Over at Connecting the dots … Jakob Scott describes an art (and book) project involving histology slides:

A project he began, called My Sarcoma, during which Ray painted over the top of his OWN histology images, transformed Ray from a sick and dying patient back into a living and vibrant artist.

From http://cancerconnector.blogspot.co.uk/2015/04/healing-art-of-pathology.html

An example of collaborative art:

Each of the paintings that Ray has made during this journey has had more than just Ray’s hands involved. Indeed, to make the paintings as you see them, a surgeon had to cut out his tumor, a pathologist had to stain and mount the tissue and a screen printer had to prepare the canvas.

Inspiring!

Florian

Science

Inferring tumour evolution 6 – What do we talk about when we talk about a clone?

Series on Tumor Evolution

What do you picture when you hear the word ‘clone’? A white-clad imperial stormtrooper from Star Wars: Attack of the clones? Or a fluffy sheep called Dolly? Both are good choices. Both are good, solid, well understood clones. But how is the situation in cancer? This is where it gets difficult. In most talks (at least the ones I sit in) the word ‘clone’ is used very loosely like it was a trivial concept. My goal for today is to show that reality is more complex than the ‘plain vanilla’ version that is often described on some introductory slide.

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Science

How normal is normal? Surprising mutations in normal-looking prostate tissue

Series on Tumor Evolution

ResearchBlogging.org

“Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue,” is the title of another recent paper that caught my attention.

I like long titles, because they often already contain the full story without the bothersome detail of the rest of the paper. Let’s look at the pieces of this one; two things stand out:

First of all, prostate cancer is generally multifocal, which means that cancer develops in different regions of the prostate, and the authors have found independent clonal expansions for these different foci. So it is not that the cancer started in one spot and then spread, these different tumors in the prostate developed independently from each other.

Morphologically normal is not always genetically normal

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Books, Science

The Emperor of All Maladies — now on Television

Science announces:

Based on the 2010 book by Siddhartha Mukherjee (Science, 22 April 2011, p. 423), this three-part documentary weaves together a sweeping history of cancer with intimate stories of contemporary patients. Told largely through interviews with researchers and oncologists, the series highlights Sidney Farber’s efforts to galvanize a national “war on cancer” in the 1940s, delves into the development of targeted drug compounds in the late 20th century, and explores the promise of personalized immunotherapies.

Science

The biggest problem in cancer evolution? That mostly people like me are doing it.

Series on Tumor Evolution

Do you know how I ended up working on cancer evolution? I would like to say it was deep thinking, profound insights and scientific vision that led me there, but -alas- the truth is that I was just really bad at proposing interesting projects to one of my first postdocs.

“Evolution? What’s that? Darwin and his finches? Forget it!”

Every time I said ‘How about integrating copy number and gene expression’ or ‘How about reconstructing networks from expression profiles’ he answered politely: “Yes, that sounds very interesting, but I would rather do evolution.”

“Evolution?” I said. “Like Darwin and his finches? Forget it! I don’t think we have that in cancer!” I said. “Be sensible and don’t ruin your career. Do genomics, like I tell you. That’s the future!” I said.

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Science

Cancer heterogeneity and evolution – the review to end all reviews

Series on Tumor Evolution

“A particular successful guide to understanding and modeling cancer progression has been evolutionary theory, which has a long tradition in cancer research. Already 40 years ago, seminal work established an evolutionary view of cancer (Nowell 1976; Dexter et al. 1978; Fidler 1978), in which carcinogenesis is regarded as an evolutionary process driven by stepwise somatic mutations and clonal expansions,”

write the authors of an awesome new review paper titled Cancer evolution: mathematical models and computational inference. (Obviously, I am not biased at all. I would call it ‘awesome’ even if I wasn’t one of the authors – I swear!)

Writing the review article made me wonder how the long tradition of an evolutionary understanding of cancer plays out on PubMed. Using code by R-psychologist I plotted the following figure, which shows the number of PubMed hits for queries on ‘cancer evolution’ (red), ‘cancer heterogeneity’ (yellow), as well as reviews on these topics (green). You can find my complete analysis as an R markdown document on my webpage.

bla bla bla
Figure 1: The number of papers on pubmed on ‘cancer evolution’ (red), ‘cancer heterogeneity’ (yellow), as well as reviews on these topics (green). Code and exact PubMed queries in R markdown document on my webpage.

What is the smallest reviewable result?

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