Genetic discovery will help clinicians identify aggressive versus benign bone tumors

June 12, 2018, Wellcome Trust Sanger Institute

The first genetic marker for the bone tumour, osteoblastoma, has been discovered by scientists at the Wellcome Sanger Institute and their collaborators. Whole-genome and transcriptome sequencing of human bone tumours revealed that a genetic change that affects the transcription factor, FOS, is a hallmark mutation of osteoblastoma.

The results, published in Nature Communications, will help clinicians correctly distinguish benign osteoblastoma tumours from aggressive tumours and direct the correct treatment.

Osteoblastoma is the most common benign tumour of the , mainly affecting children and adults between the ages of 10 and 25. It is treated by surgical removal of the tumour, however the diagnosis of osteoblastoma can be challenging. Under the microscope, osteoblastoma tumours can look very similar to osteosarcoma, an aggressive form of bone cancer that requires extensive treatment, sometimes including amputation or significant surgery and chemotherapy.

In this new study, scientists from the Wellcome Sanger Institute and their collaborators at the UCL Cancer Institute and Francis Crick Institute discovered a genetic mutation that distinguishes osteoblastoma from osteosarcoma.

The team carried out whole genome and whole transcriptome sequencing on five osteoblastoma tumours and one osteoid osteoma tumour.

Researchers discovered a mutation that affects FOS, a transcription factor that turns on and off genes to ensure they are expressed in the right cell at the right time, as well as its relative, FOSB.

When the team extended their results in a study of 55 cases they found that mutations in FOS and FOSB are ubiquitous across osteoblastoma and osteoid osteoma.

To explore whether their result could be useful as diagnostic markers for osteoblastoma, scientists examined the whole genome sequences of 55 osteosarcoma cases, and found none of the samples harboured mutations in FOS or FOSB. When the team analysed over 2,500 non-osteoblastoma tumours, they again did not find similar mutations, meaning the FOS and FOSB mutations are specific to osteoblastoma.

Dr. Sam Behjati, co-lead author from the Wellcome Sanger Institute and University of Cambridge, said: "The main clinical challenge when diagnosing osteoblastoma can be to reliably distinguish these tumours from osteosarcoma. These two forms of bone require very different treatments: osteoblastoma tumours just need removing to ease symptoms, whereas osteosarcomas is treated aggressively with surgery and intensive chemotherapy. For the first time, we have discovered a specific mutation that defines osteoblastoma."

Dr. Matthew Fittall, co-first author from the Francis Crick Institute, UCL Cancer Institute and Wellcome Sanger Institute, said: "We have known for a while that FOS is involved in the progression of bone tumours, however we have not found mutations of FOS in human bone-forming tumours before. Using genomic sequencing we have shown that in FOS and its relative FOSB are diagnostic markers of osteoblastoma."

Professor Adrienne Flanagan, co-lead author from the UCL Cancer Institute and Royal National Orthopaedic Hospital NHS Trust, said: "Genomics is transforming our understanding of cancers. Our discovery of the genetic mutation that characterises osteoblastoma will help clinicians diagnose it with more confidence and direct the correct treatment."

Explore further: Existing drugs could benefit patients with bone cancer, genetic study suggests

More information: Matthew W. Fittall et al, Recurrent rearrangements of FOS and FOSB define osteoblastoma, Nature Communications (2018). DOI: 10.1038/s41467-018-04530-z

Related Stories

Existing drugs could benefit patients with bone cancer, genetic study suggests

June 23, 2017
A subgroup of patients with osteosarcoma - a form of bone cancer - could be helped by an existing drug, suggest scientists from the Wellcome Trust Sanger Institute and their collaborators at University College London Cancer ...

Novel mutations define two types of bone tumor

October 27, 2013
Scientists have made a rare discovery that allows them to attribute two types of tumour almost entirely to specific mutations that lie in two related genes.

First seeds of kidney cancer sown in adolescence

April 12, 2018
The earliest critical genetic changes that can lead to kidney cancer have been mapped by scientists. The first key genetic change occurs in childhood or adolescence, and the resulting cells follow a consistent path to progress ...

New drug hope for rare bone cancer patients

October 12, 2017
Patients with a rare bone cancer of the skull and spine - chordoma - could be helped by existing drugs, suggest scientists from the Wellcome Trust Sanger Institute, University College London Cancer Institute and the Royal ...

Study reveals every bowel tumor and bowel cancer cell have unique genetic fingerprints

April 11, 2018
New research on bowel cancer has shown that every tumour is different, and that every cell within the tumour is also genetically unique. In the first study of its kind, researchers from the Wellcome Sanger Institute, UK and ...

Immunotherapy treatment option for selected breast cancer patients, genetic study suggests

September 13, 2017
Immunotherapy drugs could help some breast cancer patients based on the genetic changes in their tumours, researchers at the Wellcome Trust Sanger Institute and their collaborators find. Published today (13 September) in ...

Recommended for you

First immunotherapy success for triple-negative breast cancer

October 21, 2018
There is new hope for people with an aggressive type of breast cancer, as an immunotherapy trial shows for the first time that lives can be extended in people with triple-negative breast cancer.

Healthy diets linked to better outcomes in colorectal cancer

October 20, 2018
Colorectal cancer patients who followed healthy diets had a lower risk of death from colorectal cancer and all causes, even those who improved their diets after being diagnosed, according to a new American Cancer Society ...

Why some cancers affect only young women

October 19, 2018
Among several forms of pancreatic cancer, one of them specifically affects women, often young. How is this possible, even though the pancreas is an organ with little exposure to sex hormones? This pancreatic cancer, known ...

Scientists to improve cancer treatment effectiveness

October 19, 2018
Together with researchers from the University of Nantes and the University of Reims Champagne-Ardenne in France, experts from the National Research Nuclear University MEPhI have recently developed a quantum dot-based microarray ...

Mutant cells colonize our tissues over our lifetime

October 18, 2018
By the time we reach middle age, more than half of the oesophagus in healthy people has been taken over by cells carrying mutations in cancer genes, scientists have uncovered. By studying normal oesophagus tissue, scientists ...

Study involving hundreds of patient samples may reveal new treatment options of leukemia

October 17, 2018
After more than five years and 672 patient samples, an OHSU research team has published the largest cancer dataset of its kind for a form of leukemia. The study, "Functional Genomic Landscape of Acute Myeloid Leukemia", published ...

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.