Overactive Gene Found in Many Advanced Cancers

The gene for human epidermal growth factor receptor 2 (HER2) codes for a protein that promotes the growth of cancer cells.

In around 20% of breast cancers, a mutation in the gene causes cancer cells to make too much HER2 protein and this same mutation and the higher protein levels that result, occur in many types of cancer.


Scientists at the Kimmel Cancer Center (Philadelphia, PA, USA) examined more than 2,000 tumors, and found HER2 gene irregularities in 14 different advanced solid tumors. They described their findings as both clinically and scientifically good news as it could mean Herceptin and other anti-HER2 cancer therapies that are already in clinical use might help patients with some of these tumors.

A team of scientists at the cancer diagnostics company Foundation Medicine (Cambridge, MA, USA) screened the 2,223 solid tumor specimens from 20 different advanced cancers, for more than 182 genes alterations known to be linked to cancer. The results showed HER2 alterations in 14 types of solid tumor. Of these, 29% were esophageal cancer samples, 20% were uterine, 14% were breast, 12% were stomach, and 6% were lung.

They also found large variations in HER2 abnormalities. They found nearly 5% of samples had 116 different abnormalities, including 58% with amplifications, 25% with substitutions, 14% with insertions or deletions, 2% with splice site variants, 2% with translocations, and 5% with more than one alteration. Two of the tumors had both HER2 substitution and amplification.

The results add weight to the growing idea of "genome-driven therapy," where the genome profile of the tumor, rather than where it develops, is more important when considering how best to treat the individual patient's cancer. Massimo Cristofanilli, MD, FACP, director of the Jefferson Breast Center at the Kimmel Cancer Center, said, “No one ever thought that there would be such a variety of genomic alterations in HER2 in this many solid tumors.”

Prof. Cristofanilli added, “These studies highlight the need to study a broad range of genes at a high level of sensitivity and specificity when searching for novel targets of therapy. Widespread use of this approach could provide more treatment options and enable more rapid accrual to ongoing and planned trials of agents targeting pathways under study.” The study was presented at the annual meeting of the American Society of Clinical Oncology (ASCO), held May 31 to June 4, 2013 in Chicago (IL, USA).

Related Links:
Kimmel Cancer Center
Foundation Medicine