A team of researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City has published a very significant article in the journal Nature Genetics entitled "The mutational landscape of adenoid cystic carcinoma". Led by Dr. Timothy Chan, the team performed DNA sequencing on 60 cases of ACC, looking across the entire genomes for alterations that might be driving the disease. The key findings were:

 

• ACC has a "quiet" genome with relatively few alterations compared to most tumor types. Although no cancer is simple to stop, simpler tumors may be targeted more effectively than complex tumors with "noisy" genomes.
• As in prior studies, the oncogene MYB was altered in the majority of ACC cases, indicating its primary role in the disease. Secondary clusters of genetic alterations were identified that may facilitate the matching of targeted therapies to ACC patient subsets.
• Chromatin regulators were mutated in 35% of ACC tumors, pointing to epigenetic disruptions in many cases. These genes handle the machinery of DNA packaging and expression.  
• The FGF-IGF-PI3K pathway was altered in 30% of ACC tumors. These gene families are growth factors that often are implicated in cancer. 
• The NOTCH pathway was altered in 13% of ACC tumors. This gene can act as both an oncogene and a tumor suppressor. 

 

The MSKCC study provides important context for ACC patients seeking improved treatments. Extensive efforts are under way to inhibit MYB directly with drugs, but they have yet to bear fruit. In the meantime, patients with progressive ACC may wish to consult with their physicians about tumor profiling to identify secondary genetic alterations. Each tumor will have its own blend of genetic alterations driving its progression. With this study, we now understand that subsets of ACC tumors are likely to include molecular targets related to MYB, chromatin regulators, FGF, IGF, PI3K and NOTCH. Fortunately, there is a growing list of drugs in development that inhibit these targets. Indeed, one of the current clinical trials for ACC patients inhibits the receptors of FGF.

 

The study was funded primarily by the National Institutes of Health (NIH), including the National Institute of Dental and Craniofacial Research (NIDCR). Dr. Chan and his colleagues are analyzing the tumors of an additional 50 ACC patients to depict further the landscape of ACC genomics. The MD Anderson Cancer Center, the Wellcome Trust Sanger Institute, Johns Hopkins University and TGEN also will be publishing DNA sequencing data soon, bringing the number of ACC cases with extensive genomic characterization to more than 200, a remarkably high number for a rare cancer. ACCRF has supported all these efforts.

 

Note: Patients should not confuse the terms "genetic" and "inherited". ACC, like all cancers, is viewed as a "genetic" disease in that altered genes lead to uncontrolled growth of previously-normal cells. However, ACC is not "inherited" because the genetic alterations are acquired during the patient's lifetime in one initiating cell, not handed down from parental DNA found in all cells. Some cancers are heavily influenced by heredity, but that is not the case with ACC. 

 

2013 ACC Survivor Meeting

ACCRF Board of Directors Jeff & Marnie Kaufman, Kara Gelb, Ralph Mollis & Douglas Meyer

That same evening, the 7^th Annual Friends of ACCRF event drew a record 240 people and raised over $55,000!  In addition to a wide range of friends and family, this year's fundraiser attracted scores of patients and ACC researchers, who traveled from 10 states to be a part of the special evening. The event featured food, music, an auction and a lot of fun.  Most importantly, every dollar raised goes directly to support ACC research.