Improved analysis of kidney cancer

August 11, 2017, Lund University

Every year, just over 1000 people are diagnosed with kidney cancer in Sweden. The three most common variants are clear cell, papillary and chromophobe renal cancer. Researchers compare the gene expression in tumour cells from a kidney cancer patient with cells from healthy tissue to figure out in which part of the kidney the cancer began and what went wrong in these cells. Now, a research team at Lund University in Sweden has discovered that in the Cancer Genome Atlas database, the gene expression in reference samples from normal tissue varies, depending on where in the kidney the samples happen to have been taken. The analyses can be improved by clarifying which samples correspond to the correct tissue. The study has now been published in Cell Reports.

The part of the which purifies the blood and generates urine is called the nephron and functions as a kind of tubing system. Each kidney contains around a million nephrons which collectively filter 180 litres of primary urine (waste products, water and salts) every day. This results in 1.5 litres of concentrated liquid, which is excreted through urination.

"Everything is very specifically regulated and the cells have different and hence properties depending on their location in the tubing.", explains Håkan Axelson, research team leader and professor of molecular biology.

When a tumour biopsy is taken from a patient and compared with healthy kidney tissue, it serves to map how the various are expressed so as to clarify what has gone wrong in the tumour cells. The Cancer Genome Atlas – an international database containing almost 1000 samples from kidney tumours and healthy tissue – is a tool in this process.

"But when our research team studied the samples from the database, we noticed a great range of gene expressions between normal tissue samples. It emerged that the samples in the Cancer Genome Atlas were taken at different depths in the kidney and therefore contain different types of cells, which means that their gene expressions also vary", says Håkan Axelson.

Unreliable and sometimes completely incorrect comparison

The normal reference samples thus contain various types of cells depending on where in the kidney they happen to have been taken. Since the Atlas does not state the location in the kidney the reference sample was collected, the comparison risks being unreliable and sometimes completely incorrect.

"Since the gene expression in the cells varies depending on their location, it is important that the normal samples contained in the database should also be taken from the location corresponding to that of the patient's tumour", says David Lindgren, who is the lead author of the study.

As an example, it was previously suspected that clear cell tumours occur in the first part of the nephron, but if these are compared with a normal sample taken deeper inside the nephron, the cells will not correspond to the tumour . The gene is thereby different. Although each patient is unique, the various types of tumours have different specific genetic changes which occur as a consequence of properties in the cell in which the tumour originated.

"It is extremely important to know what characterises the in which the tumour occurs. Through better understanding of this interaction, we can increase our understanding of the course of the disease, which could be significant for diagnostics and, in the longer term, also for the choice of treatment", concludes Håkan Axelson.

Explore further: Study discovers proteins which suppress the growth of breast cancer tumors

More information: David Lindgren et al. Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes, Cell Reports (2017). DOI: 10.1016/j.celrep.2017.07.043

Related Stories

Study discovers proteins which suppress the growth of breast cancer tumors

June 12, 2017
Researchers at the University of Birmingham have found that a type of protein could hold the secret to suppressing the growth of breast cancer tumours.

Kidney tumors have a mind of their own

November 21, 2012
New research has found there are several different ways that kidney tumours can achieve the same result – namely, grow.

New genetic cause of childhood cancer found

May 30, 2017
Scientists have identified a genetic mutation that causes a childhood kidney cancer called Wilms' tumour.

A 'key' to metastasis formation

July 13, 2016
Researchers at Hokkaido University in Japan have demonstrated that a molecule called biglycan plays an intrinsic role in attracting tumour cells toward the inner wall of tumour blood vessels.

Tumor-trained T cells go on patrol

May 15, 2017
'Tumour-trained' immune cells - which have the potential to kill cancer cells - have been seen moving from one tumour to another for the first time. The new findings, which were uncovered by scientists at Australia's Garvan ...

Highly prevalent gene variants in minority populations cause kidney disease

March 1, 2017
African Americans have a heightened risk of developing chronic and end-stage kidney disease. This association has been attributed to two common genetic variants - named G1 and G2—in APOL1, a gene that codes for a human-specific ...

Recommended for you

Researchers decipher the genome in chronic lymphocytic leukaemia

May 23, 2018
A team of researchers from University of Barcelona (UB) and their collaborators report for the first time the complete epigenome of chronic lymphocytic leukaemia, the most common type of leukaemia. The study, published in ...

Scientists discover how breast cancer hibernates: study

May 22, 2018
Scientists have identified the mechanism that allows breast cancer cells to lie dormant in other parts of the body only to reemerge years later with lethal force, according to a study published Tuesday.

Researcher: Big data, networks identify cell signaling pathways in lung cancer

May 22, 2018
A team of scientists led by University of Montana cell biologist Mark Grimes has identified networks inside lung cancer cells that will help understand this cancer and fight it with drug treatments.

Resetting the epigenetic balance for cancer therapy

May 22, 2018
Though mutations in a gene called MLL3 are common across many types of cancers, their relationship to the development of the disease has been unclear. Now, a Northwestern Medicine study has identified an epigenetic imbalance ...

Downward-facing mouse: Stretching reduces tumor growth in mouse model of breast cancer

May 22, 2018
Many cancer patients seek out gentle, movement-based stretching techniques such as yoga, tai chi and qigong, but does stretching have an effect on cancer? While many animal studies have attempted to quantify the effects of ...

Compound in citrus oil could reduce dry mouth in head, neck cancer patients

May 21, 2018
A compound found in citrus oils could help alleviate dry mouth caused by radiation therapy in head and neck cancer patients, according to a new study by researchers at the Stanford University School of Medicine.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.