Mutations May Help Identify Laryngeal Tumors with Favorable Prognosis

Researchers have identified mutations that may help distinguish which laryngeal cancer patients could benefit from therapy, since the disease is notoriously resistant to chemotherapeutic treatments.

It now may be possible to better categorize patients with laryngeal cancer. Researchers are reporting they have identified two new subtypes of laryngeal cancer that appear to be linked to different survival outcomes. In a study published in the journal Nature Communications, a team of investigators from Fox Chase Cancer Center and Johns Hopkins University School of Medicine report the new findings may affect patient stratification and prognostication.

The researchers combined somatic mutations, gene expression, chromosomal copy number, and methylation data to classify head and neck patients. As part of this investigation, they analyzed molecular and clinical data from 256 head and neck cancer patients available in The Cancer Genome Atlas (TCGA).

“This is one of the first studies showing differential behavior of laryngeal cancer from other forms of head and neck cancer, suggesting we should be cautious about thinking of these as a single disease type,” said study investigator Suraj Peri, PhD, who is an assistant research professor at Fox Chase Cancer Center in Philadelphia, Pennsylvania.

The researchers found mutations that damage histone methyltransferase NSD1 or NSD2 are associated with significantly longer survival in laryngeal cancer patients. Peri said these results were surprising because no such association was found in non-laryngeal forms of head and neck cancer, such as oral cancer. “Earlier studies including the original Nature publication from TCGA had indicated no prognostic differences in HPV-negative head and neck cancer subtypes. Our classification differs from TCGA classification, which is based on gene expression, suggesting the value of a more integrative analysis,” Peri told OncoTherapy Network.

The current investigation included clinical information (follow-up and new tumor event data) for 526 samples (including 256 samples from TCGA). Peri said the role of NSD mutations in various forms of cancer should be investigated in larger independent cohorts, and his team is currently working to elucidate the functional roles of NSD1 and NSD2 in laryngeal cancer. 

The authors note that squamous cell carcinomas of the head and neck are highly heterogeneous and occur in multiple anatomical sites. These cancers, including laryngeal cancer, are notoriously resistant to chemotherapeutic treatments and radical treatment options for laryngeal cancer often result in low quality of life and adverse side effects. 

Peri said currently, there are no reliable prognostic biomarkers for laryngeal cancer. However, results from this current study suggest that NSD1 or NSD2 can be used for guiding therapy. In addition, these proteins may serve as therapeutic targets. “We hope that our biomarker results would help treatment decisions in selecting strong candidates for organ preservation and protect patients from therapeutic consequences,” said Peri.