Revelations offer a different way to view tumors and, ultimately, develop treatments
(From the June 2018 issue of Research Now)
Cancers have traditionally been classified by where they start — breast cancer or colon cancer — but the recently completed PanCancer Atlas is a different way to look at tumors.
“The PanCancer Atlas looks across cancers and compares lung cancer to breast cancer to testicular cancer to find commonalities in their cells of origin, oncogenic processes and oncogenic pathways,” says Julie Gastier-Foster, PhD, a senior director at the Institute of Genomic Medicine, vice chair of Laboratory Genetics in the Department of Pathology and Laboratory Medicine, and atlas contributor.
Nationwide Children’s Biospecimen Core Resource (BCR), which Dr. Gastier-Foster oversees, is the center that accepted, managed and distributed tumor samples, healthy tissue samples and clinical data from more than 10,000 cancer patients to National Institutes of Health-funded researchers.
To increase quality and efficiency, the BCR optimized a nucleic acid extraction method to obtain DNA and RNA from the same tissue.
BCR faculty also developed an identity panel, a $20 test that prevented them from sending tissue from the same tumor out for genomic sequencing twice. Sequencing a sample cost $25,000 to $30,000 and with so many specimens to manage, mistakes occasionally occurred and occasionally two tissue suppliers submitted tumor samples from the same person.
Researchers at institutions across the United States performed detailed analyses of the genomic, molecular, imaging and clinical data and discovered commonalities and associations.
The results suggest that, independent of where the tumors originated, 33 tumor types could be reclassified as 28 types, or “clusters,” based on their cellular and genetic makeup.
“Breast cancer, ovarian cancer and cervical cancer overlap — we don’t know why — but it can be that one drug can work for multiple tumor types,” says Dr. Gastier-Foster, who is also a clinical professor of pediatrics and pathology at The Ohio State University College of Medicine.
Among their findings, atlas researchers suggest:
- Tumor types cluster by their possible cells of origin
- Inherited and acquired mutations, influence of the tumor’s underlying genome and epigenome on gene and protein expression, and the interplay of tumor and immune cells are critical to cancer development and progression
- Patterns of cancer vulnerabilities may be found in genomic alterations in the signaling pathways that control cell cycles, growth and death
These findings, NIH officials say, will aid in the development of further studies and treatments.
Dr. Gastier-Foster says the benefits to patients can take several years but insights provided by detailed genomics studies pay off.
She pointed to a study co-led by Shalini Reshmi, PhD, a clinical director within the Institute for Genomic Medicine. Dr. Reshmi and colleagues here and across North America, including Dr. Gastier-Foster, characterized the genomic alterations from more than 1,300 children with Philadelphia chromosome-like acute lymphoblastic leukemia (ALL). From the information, oncologists now use targeted therapies.
Children, adolescents and young adults with this aggressive form of ALL have traditionally suffered very poor outcomes. Now, “every time we identify this in a child, their prognosis for survival jumps from 20 percent to 70 to 80 percent,” Dr. Gastier-Foster says. “That’s why we do this work.”
The PanCancer Atlas is published as a collection of 27 papers in Cell and related journals, summing up the work of The Cancer Genome Atlas, more than 30 cancer-specific papers published during the last decade (with more to come).
All the information from the PanCancer Atlas is now available to researchers through the National Cancer Institute’s Genomic Data Commons repository.