Researchers Use Next Generation Sequencing to Discover Extensive Mutations in Sarcoma Patients

Chinese researchers have used next generation sequencing to identify different molecular profiles in pediatric and adult patients with sarcomas. The findings were shared in an abstract presented recently at the 2022 American Association of Cancer Research Annual Meeting.

The findings are important in that the discoveries pointed to gene mutations that could be targeted in the treatment of these sarcomas by drugs already approved by the U.S. Food and Drug Administration.

What Is Next Generation Sequencing?

Next generation sequencing is a new technology with decided benefits, resulting in improved throughputs, speed and scalability. It’s used to identify the order of nucleotides within either targeted regions of RNA or DNA or entire genomes.

Next generation sequencing has dramatically changed biological science, providing labs with new tools that have broad applications. For example, next generation sequencing can be used to discover novel RNA variants and the site of splices. As with the Chinese study, the technique can also sequence cancer samples to study variants and tumor subclones. It can be used to identify novel pathogens and study the human microbiome.

Challenges in Identifying and Treating Sarcomas

There are more than 100 subtypes of pediatric sarcomas, which represent 12 percent of all pediatric cancers. While there are some available molecular detection technologies to use in the diagnosis and treatment of pediatric sarcoma, it remains a challenging cancer. Those difficulties are largely due to limited biopsy specimens and overlapping morphological features among the subtypes.

Researchers in the study used next generation sequencing to analyze samples of 700 Chinese patients with pediatric or adult sarcomas. The researchers developed molecular profiles by testing both tumor tissue and blood specimens using the Onco Panscan plus DNA and RNA sequencing panel produced by Genetronhealth.

The samples included 224 from children and 476 from adults. The most common tumor types in children were rhabdomyosarcoma (54 samples), Ewing’s sarcoma (22) and osteosarcoma (34). In adults, the most prevalent sarcomas were angiosarcoma (18 samples) and fibrosarcoma (17).

Extensive Mutations Found in Adult, Child Samples

In children, researchers found a mean of 3 mutations per patient. The most frequent alterations were missense mutations (326), fusions (129) and copy number variants (66). Mutations were most commonly found on the TP53 (29), EWSR1 (20) and ALK genes (15).

In adults, there was a mean of 5 mutations per patient. The most common alterations were missense mutations (1,438), fusions (221) and truncating mutations (215). The most frequently mutated genes were TP53 (140), NF1 (23) CTNNB1 (20) and RB1 (20).

Pathological subtypes were confirmed in 40.2 percent (90) and 48.1 percent of children and adults, respectively. In addition, researchers found 72 drug-targeted gene mutations in 57 pediatric patients, 35 of which (48.6 percent) could be targeted by drugs approved by the FDA. In adults, there were 256 drug-targeted genes detected, with actional mutations by drug therapies at 78.9 percent (202).

The findings illustrate the impact next generation sequencing has had on the identification and treatment of cancer and other diseases. Next generation sequencing has provided dramatic technology advances in genomic profiling by identifying biomarkers and providing better insights into prognoses and responses to therapies in multiple cancers.

For example, a recent article in  JAMA Oncology noted that next generation sequencing could accurately locate the site of cancer origin in patients with a previously unknown disease status. The findings help identify clinical treatments via targeted drug therapies in those patients.

“The genomic landscape of pediatric sarcomas is different from that of adults,” the researchers concluded. “[Next generation sequencing] aids in the subtype classification and clinical guidance of pediatric sarcomas, providing evidence for personalized treatments with clinical benefit.”