NIH researchers use genomics to set squamous cell carcinomas apart from other cancers
Results could advance treatments for head and neck and other cancers.
Researchers supported by the National Institutes of Health have uncovered molecular characteristics that link the genomic profiles of squamous cell carcinomas (SCCs) from five areas of the body and that set these SCCs apart from other cancers. Using a robust dataset of SCCs from the head and neck, lung, esophagus, cervix, and bladder, the researchers also found defining characteristics in subtypes of SCCs associated with tobacco use or human papillomavirus (HPV) infection. This research may lead to more effective diagnosis and treatment of these cancers by helping researchers develop tailored strategies for specific cancer subtypes.
Published in Cell Reports, the study was led by Carter Van Waes, M.D., Ph.D., and his colleague Zhong Chen, M.D., Ph.D., from the Head and Neck Surgery Branch of NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD). They collaborated with teams of researchers across the United States and Canada through The Cancer Genome Atlas (TCGA) consortium, a joint effort of the NIH’s National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI).
The study is one of 27 papers published in Cell journals this month, that describe important results from the PanCancer Atlas, a detailed analysis from a dataset containing molecular and clinical information on more than 10,000 tumors from 33 forms of cancer. The PanCancer Atlas is a culmination of more than a decade of work by more than 150 TCGA researchers at institutions across North America.
The new SCC study expands upon research reported by TCGA researchers in 2014 and 2015, which compared genomic features of SCCs in head and neck cancer associated with smoking or HPV. Researchers found that certain features were present in tumors associated with both smoking and HPV, while others were exclusive to only one of the two. They also found similarities in the genomic characteristics of head and neck cancers with lung cancers, some bladder cancers, and cervical cancer.
Head and neck cancers and their treatments can cause severe problems with talking, chewing, and swallowing, and 90 percent of these cancers are SCCs. Tobacco use is one of the leading risk factors for head and neck cancers, according to NCI. Certain strains of HPV—especially HPV type 16, which is also associated with cervical cancer—are risk factors for some types of head and neck cancers. The incidence of HPV-related head and neck cancers has grown in recent years.
“We need better ways to treat head and neck cancers so we can preserve patients’ voices and improve their quality of life,” said Van Waes, NIDCD clinical director and chief of the NIDCD Head and Neck Surgery Branch. “These findings provide us with important insights into these cancers and some squamous cell cancers in other areas of the body that will help us target pathways for prevention and treatment.”
For the current study, the researchers used new analytic tools to delve deeper into the similarities and differences among SCCs in the head and neck, lung, esophagus, cervix, and bladder. Using the recently completed PanCancer Atlas, the researchers combined multiple platforms of genomic data from 1,400 SCC samples into integrated analyses, which created visual clusters of tumors based on their genomic characteristics.
The researchers found that SCCs in the five areas studied have certain similar genomic features that set them apart from other types of cancers. The most common shared alterations are gains or losses of the sections of certain chromosomes (where DNA is packaged), which make it likely that these regions harbor genes important in the development of SCCs. Importantly, these changes affect the expression of many more genes than previously believed, enabling new avenues for research.
The researchers also found that the subsets of SCCs associated with smoking and HPV have distinct genomic signatures. SCCs associated with HPV tend to have fewer of the gains or losses in sections of chromosomes; instead, HPV-associated tumors have mutations in the DNA or other chemical (epigenetic) modifications in certain genes.
“Analyses on this scale are only possible with a large dataset such as PanCancer Atlas and the tireless efforts of more than 50 researchers involved in looking at squamous cell cancers,” added Chen.
This research was supported by the following NIH grants: NIDCD intramural project grant ZIA‐DC‐000074; NHGRI grants U54 HG003273, U54 HG003067, and U54 HG003079; and NCI grants U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, and P30 CA016672.
About the National Institute on Deafness and Other Communication Disorders (NIDCD): NIDCD supports and conducts research and research training on the normal and disordered processes of hearing, balance, taste, smell, voice, speech, and language and provides health information, based upon scientific discovery, to the public.
About the National Cancer Institute (NCI): NCI leads the National Cancer Program and NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers.
About the National Human Genome Research Institute (NHGRI): NHGRI is the driving force for advancing genomics research at the National Institutes of Health. By conducting and funding world-class genomics research, training the next generation of genomics experts, and collaborating with diverse communities, NHGRI accelerates scientific and medical breakthroughs that improve human health.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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