Genomics offers new treatment options for infants with range of soft tissue tumors

June 18, 2018, Wellcome Trust Sanger Institute
Credit: CC0 Public Domain

The genetic causes of a group of related infant cancers have been discovered by scientists at the Wellcome Sanger Institute, the University of Wuerzburg and their collaborators. Whole genome sequencing of tumours revealed mutations which are targetable by existing drugs used to treat lung cancer and melanoma.

The results, published today (18 June) in Nature Communications have implications for clinical practice and the diagnosis of rare cancers in , and could lead to new, targeted treatment options for these children.

Each year in the UK, over 100 infants under the age of one are diagnosed with rare cancerous tumours in their soft tissues. One of these soft cancers, known as congenital mesoblastic nephroma (CMN), is the most common kidney diagnosed in early infancy. Occasionally spotted as a lump in utero during an ultrasound scan, these tumours are diagnosed definitively after birth. Treatment involves surgical removal of the tumour and sometimes chemotherapy, both of which can damage surrounding tissues at a critical time in life.

The underlying these infant cancers are unclear, with over 30 per cent of cases of CMN having no known driving the .

In a new study using samples from archives in Germany and Great Ormond Street Hospital, London, scientists from the Wellcome Sanger Institute and their collaborators sequenced the whole genomes and transcriptomes of 17 CMN tumours, and extended their findings to a total of 350 cases, including CMN and five related soft tissue tumour types: infantile fibrosarcoma (IFS), nephroblastomatosis, Wilms tumour, malignant rhabdoid tumour and clear cell sarcoma of the kidney.

Researchers discovered at least one, if not two genetic changes in each of the tumours that were driving the cancer. In particular, the genetic data revealed mutations in the Epidermal Growth Factor Receptor (EGFR) in CMN tumours, and both CMN and IFS tumours had mutations in the BRAF gene.

The EGFR mutation identified is targeted by an existing EGFR inhibitor drug called afatinib, used to treat , whereas drugs designed to treat melanoma skin cancer target BRAF. It is possible that these existing drugs could help infants with soft tissue tumours, based on their mutations.

Dr. Sam Behjati, co-lead author from the Wellcome Sanger Institute and University of Cambridge, said: "We have discovered new diagnostic markers for soft tissue cancers in infants, including CMN, in which the genetic cause of the disease was unknown in one third of patients. These results indicate which existing drugs could be used to help children overcome these tumours in infancy."

Dr. Grace Collord, co-first author from the Wellcome Sanger Institute and University of Cambridge, said: "Sequencing the whole genomes and transcriptomes of these related cancers showed that while anatomically these cancers appear different, genetically they are very similar. We found mutations affecting EGFR and BRAF, both of which are targets for existing drugs. If infants with very large soft tissue tumours could be treated with these targeted agents, there's a chance it could shrink the tumour enough that the necessary surgery would be less damaging."

Professor Manfred Gessler, co-lead author from the University of Wuerzburg, said: "Genomics is changing how we do health research. The genetic diagnostic markers discovered in this study can be readily integrated into routine to give confident diagnoses and match patients with soft tissue tumours to the most appropriate clinical trial, helping to make the trials more effective and ultimately help these children."

Explore further: Genetic discovery will help clinicians identify aggressive versus benign bone tumors

More information: Jenny Wegert et al, Recurrent intragenic rearrangements of EGFR and BRAF in soft tissue tumors of infants, Nature Communications (2018). DOI: 10.1038/s41467-018-04650-6

Related Stories

Genetic discovery will help clinicians identify aggressive versus benign bone tumors

June 12, 2018
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 ...

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 ...

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 ...

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 ...

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 picks out children with incurable brain cancer who could benefit from adult therapy

May 14, 2018
Children with incurable brain tumours could benefit from potentially life-extending treatment if genetic testing was used to personalise therapy as it is in many adults, major new research reports.

Recommended for you

Colon cancer is caused by bacteria and cell stress

September 19, 2018
Researchers at Technical University Munich have reported findings related to the development of colon cancer. "We originally wanted to study the role of bacteria in the intestines in the development of intestinal inflammation," ...

Researchers find adult stem cell characteristics in aggressive cancers from different tissues

September 19, 2018
UCLA researchers have discovered genetic similarities between the adult stem cells responsible for maintaining and repairing epithelial tissues—which line all of the organs and cavities inside the body—and the cells that ...

Ketogenic diet reduces body fat in women with ovarian or endometrial cancer

September 19, 2018
Women with ovarian or endometrial cancer who followed the ketogenic diet for 12 weeks lost more body fat and had lower insulin levels compared to those who followed the low-fat diet recommended by the American Cancer Society, ...

Could the zika virus fight the brain cancer that killed john McCain?

September 18, 2018
(HealthDay)—Preliminary research in mice suggests that the Zika virus might be turned from foe into friend—enlisted to curb deadly glioblastoma brain tumors.

Eating foods with low nutritional quality ratings linked to cancer risk in large European cohort

September 18, 2018
The consumption of foods with higher scores on the British Food Standards Agency nutrient profiling system (FSAm-NPS), reflecting a lower nutritional quality, is associated with an increased risk of developing cancer, according ...

CRISPR screen reveals new targets in more than half of all squamous cell carcinomas

September 18, 2018
A little p63 goes a long way in embryonic development—and flaws in p63 can result in birth defects like cleft palette, fused fingers or even missing limbs. But once this early work is done, p63 goes silent, sitting quietly ...

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.