Genomics contributes to battles against cancer

Genomics is continuing the battle against cancer, with a large number of studies in recent months cataloging everything from frequently mutated genes to predictors for breast cancer. Here’s a rundown of some of the most important findings.

Recurrent cutaneous melanoma alterations

A study in Nature Cancer from a team of US and Canadian researchers has identified frequently mutated genes and other informative features of tumors.

The study may offer insights into disease treatments and treatment outcomes.

Looking at more than 1,000 melanoma exomes, the team discovered significantly mutated genes with co-occurring loss-of-heterozygosity and loss-of-function mutations and significantly mutated genes on the X chromosome in males.

“Our multi-omic analysis provides insights into melanoma etiology and supports contribution of specific mutations to the sex bias observed in this cancer,” the authors wrote.

Predicting recurrence in triple-negative breast cancer

A report from JAMA Oncology explained how a combined method measuring both circulating tumor DNA and circulating tumor cells can detect lingering residual disease, post-neoadjuvant chemotherapy, in women with early-stage triple-negative breast cancer, and it can also predict disease recurrence.

The study noted that these patients often receive that treatment and while some see no recurrence, a significant number do. Blood-based genomic testing has quickly become popular for identifying women with residual cancer and whose outcome could improve with new or existing treatments.

“In this preplanned secondary analysis of a randomized clinical trial, detection of circulating tumor DNA and circulating tumor cells in patients with early-stage triple-negative breast cancer after neoadjuvant chemotherapy was independently associated with disease recurrence, which represents an important stratification factor for future postneoadjuvant trials,” the authors wrote.

Detecting cancer from cfDNA fragment patterns

A new method called EPIC-Seq (epigenetic profile inference from cfDNA deep sequencing) was presented recently at this American Association of Cancer Research’s annual meeting, reports GenomeWeb.

“The basis of the EPIC-Seq approach was a hypothesis that less protected nucleosomes should yield a more diverse population of DNA fragment lengths, because these regions have a higher chance of being cut randomly,” GenomeWeb reported. “Therefore, a measure of DNA fragment size distribution, or diversity, could be a surrogate for the nucleosomal factors previously determined to predict gene expression.”

The method, developed by researchers at Stanford, “can accurately predict tissue- and tumor-specific gene expression in plasma samples from healthy individuals and cancer patients, without knowledge of specific gene mutations or sequencing of expression products.”

It was developed using 250X genome-wide plasma DNA sequencing on a range of samples whose fragment patterns were compared with genome-wide expression data to define the relationship between the two.

Minimal residual disease monitoring for cancer recurrence

A recent study by European researchers in Science Translational Medicine described the development of an analytical method to improve circulating tumor DNA by tracking large numbers of patient-specific cancer mutations. The method could be used to test minimal residual disease and cancer recurrence.

The study notes that the analysis of tumor DNA in blood is a noninvasive method for detecting cancer and monitoring responses to therapy—blood samples are easy to obtain and may better represent mutations found in a tumor than more invasive methods. Researchers called the method INVAR—integration of variant reads.

“We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available,” researchers wrote. “As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.”

Preventing breast and ovarian cancer regardless of income level

An analysis published in the journal Cancers estimated the cost-effectiveness or population-based BRCA testing in general population women from a variety of countries in  high, upper-middle, and low-middle income categories.

Results suggested that broad-scale BRCA1/2 testing would be cost-effective for both health systems and payers if it can be done for $172 or less.

More screening would help, GenomeWeb noted, because “more than half of individuals who carry BRCA1 or BRCA2 germline variants implicated in breast or ovarian cancer do not have the requisite personal or family history of cancer that current guidelines and healthcare systems use to determine who should receive genetic testing.”

Applied to universal testing, researchers estimated that up to 2,700 breast cancer cases could be prevented for every 1 million women and up to 449 ovarian cancers per million women.