In the Lab

On Cancer: Investigators Sequence the Genome of a Rare Head and Neck Cancer

Pictured:  Timothy Chan Physician-scientist Timothy Chan

Since the completion of the Human Genome Project in 2003, many researchers have turned their efforts toward sequencing the genomes of various kinds of cancer. Collaborative groups including The Cancer Genome Atlas (TCGA), a government-funded project created to accelerate our understanding of the molecular basis of cancer, have published genomic information on lung, ovarian, and colorectal cancers, among others.

Memorial Sloan Kettering has played a role in many of these multicenter efforts, sharing both tumor samples and the expertise of its clinician-scientists. But despite these efforts, these studies only examine a small fraction of the many different types of human malignancies. Now our investigators have performed complete sequencing and analysis of a large set of a rare head and neck cancer called adenoid cystic carcinoma (ACC), which is an aggressive form of salivary gland cancer.

“Sequencing rare cancers such as ACC is a great way for Memorial Sloan Kettering to take the lead in unraveling cancer genomics,” says Timothy A. Chan, a radiation oncologist and investigator in the Human Oncology and Pathogenesis Program (HOPP), and the senior author of the study, which was published online May 19 in Nature Genetics. “Just as we have the specialized knowledge and experience to treat rare cancers in the clinic, analyzing their genomics is an area where we believe we can make an important contribution.”

An Enigmatic Malignancy

ACC is one of the most difficult cancers to treat. Some patients are cured by surgery alone, but the disease can return or spread to other parts of the body, and no known chemotherapy agent is effective, although many patients are treated with radiation therapy. The cancer, which affects 800 to 1,000 people in the United States annually, can recur for as many as ten to 15 years after treatment.

Until the current study, little was known about the molecular changes that lead to these cancers. The investigators sequenced 60 matched pairs: the complete genomes or exomes of tumor samples from 60 patients along with normal tissue samples from those same 60 patients.

“By comparing the mutational landscape of tumors to normal DNA and comparing tumors with other tumors, you can determine which genes are mutated in these cancers and also how these tumors can differ from one another,” Dr. Chan explains.

The investigators found that ACC tumors could be divided into three general subtypes: those with mutations in PI3-kinase pathway genes, which encode enzymes involved in cell growth and proliferation; those with mutations in chromatin remodeling genes, which control how other genes are expressed; and those with mutations in a pathway called Notch, which also modifies gene expression.

Targeted therapies are already in development for these three types of mutations in other cancers, raising hope that clinical trials for ACC could start quickly.

Quiet Genomes

The most surprising part of the discovery was that ACC tumors carry very few mutations when compared with most other solid tumors.

“We call these quiet genomes,” Dr. Chan explains. “Breast and lung cancer are very noisy, with about 100 times more mutations than ACC. This is one of the main reasons why targeted therapies for those cancers usually work for only a short time.”

Because ACC tumors have so few mutations, Dr. Chan and his colleagues expect that targeted therapies against them will be more effective than for many other cancers with similar mutations. He compares the number of mutations seen in ACC to the number in chronic myeloid leukemia, a type of blood cancer for which targeted therapies have been very effective.

“It is very unusual for a solid tumor to have so few mutations,” he adds.

Focus on Rare Cancers

The study was a collaboration among researchers in HOPP, the Department of Radiation Oncology, the Head and Neck Surgical Service, the Computational Biology Program, and investigators from a multi-institutional collaboration, including the University of Pittsburgh Medical Center and the National Cancer Center in Singapore. Several cancer centers provided tumor samples.

“It’s great that we’ve set up the infrastructure to do this kind of genome sequencing and analysis here at Memorial Sloan Kettering, because we have a lot more diseases to study,” Dr. Chan notes. The team is already working with endocrinologist and HOPP investigator James A. Fagin to sequence other rare head and neck cancers, including Hurthle cell carcinoma.

This research was funded by the National Institutes of Health under grants RO1CA154767, R21DE023229, and 5T32CA009685; the Geoffrey Beene Foundation; the STARR Cancer Consortium; the Louis Gerstner Foundation; the American Head and Neck Society/American Academy of Otolaryngology — Head and Neck Surgery Foundation; the Howard Hughes Medical Institute Medical Research Fellows Program; and the Adenoid Cystic Carcinoma Research Foundation.

Comments

I have ACC and would like any updates you have and would like to be on an email list if possible??

Hi Vickey, we recommend you get in touch with the ACC Research Foundation, at http://www.accrf.org/. Also, please check back periodically for new clinical trials here: http://www.mskcc.org/cancer-care/clinical-trials/clinical-trial. Thanks for your comment.

In 2009 I had a nodule removed from my scalp. I was informed that it was a rare cancer of a sweat gland (adenocystic carcinoma). I had two additional surgeries before clear margins were achieved. Has your research included similar cancer?

Linda, If you had an adenoid cystic carcinoma on your scalp, then this study would be relevant to your tumor. If you had another type of tumor, it would not be. Adenoid cystic carcinoma can occur many places, including the scalp. Thank you for your comment.

Any news on LMS? Please forward to me. I am a patient at Sloan.

Beverly, you can find a list of our clinical trials filtered for endometrial and other uterine cancers (including leiomyosarcoma) here: http://www.mskcc.org/cancer-care/adult/endometrial-other-uterine/clinical-trials. Please discuss your possible participation with your Memorial Sloan-Kettering doctor. Thank you for your comment!

Similar to Linda above, my sister had a tumor removed from her right scalp - she had a rare cancer of the sweat gland. She had radiation therapy as there was no known chemotherapy for her cancer. She ultimately passed away. What is the risk that a sibling may develop the same cancer?

Grace, we are sorry for the loss of your sister. For most types of cancer, only about 5-10 percent are hereditary. The rest occur randomly by chance. If you are concerned about a family history of cancer, you can learn more about our clinical genetics service here: http://www.mskcc.org/cancer-care/hereditary-genetics. Thank you for your comment.

please check out the following books :"The China Study", "Gerson Therapy", and "80 10 10" these books link food, health and cancer.... food can feed cancer or feed your body!!!

Any research being done on myoepithelial carcinoma? I had tumors, treated with radiation, now it has matastisized to the lungs.

Marsha, if you would like to speak to a physician at Memorial Sloan-Kettering about your treatment, please call 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. Thank you for your comment.

I am one year post op. Adenoid cystic carcinoma. Cribriform type with perineural invasion. Final path by Stanford. Six weeks 200 Gy rad.. completed june 12'.Would be interested in any information on this study & future trials. No sign of recurrence at this time. Thankyou!

Bonnie, we're glad to hear you're doing well. If you would like to keep up with the latest information on adenoid cystic carcinoma, we recommend you get in touch with the ACC Research Foundation at http://accrf.org/. Thank you for your comment.

A very dear friend has been diagnosed and surgically treated for apocrine sweat gland carcinoma of the face, neck and lymph nodes. Radiation will soon begin. The cancer continues to spread on his face, following surgery, with a new second procedure now scheduled, prior to radiation. What if the cancer continues, what does his future hold?

Anita, unfortunately we are not able to answer individual medical questions on our blog. If your friend would like to make an appointment to speak with a Memorial Sloan-Kettering doctor, he can call 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. Thank you for your comment.

My late wife had ACC for 24 years of our 26 years of marriage. She was diagnosed in 1981 and passed away in 2005. The original location was the gland that secretes earwax. It spread to her lungs and brain. I'm glad they are finally making progress on this cancer.

I was diagnosed with cancer of the Parotid gland at the age of 11.
I have not been able to find one other adult survivor of this type of cancer as a child. It would be helpful and supportive for me to be able to communicate with someone I can truly relate to. Thank you for being there.

My son Andrew has been diagnosed with naseopharngeal carsinoma (spelling) which I understand is more common in south Asia. He has not traveled to these areas. He is a 34 year old male with two young children ( 21/2 years old abd a 6 month old.) dHe has WV medicaid which is not accepted at many ocations. Would his case be of interest to Sloan-Kettering? We are,of course, much disturbed by the direction of his malady. He took so long to diagnose it. Symptoms appeared as early as a year ago, but has just recetly been diagnosed.

Susan, If you (or your son Andrew) would like to make an appointment with a Memorial Sloan-Kettering physician, please call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. They can also provide information (or refer you to a specialist ) regarding coverage. Thanks for your comment.

My domestic partner of 10 years, Jay (47), was just diagnosed with Ameloblastic carcinoma of his right maxilla, (post-surgery on August 12,). This was determined based on the pathology report after the tumor was removed. Initially, the Physicians thought the tumor was Squamous cell carcinoma.
We have been meeting with both medical and radiation Oncologists in Pittsburgh, PA, neither of which has ever had/treated this form of cancer before. They both indicated they will treat it as though it "were" Squamous cell.
I was hoping that perhaps someone, just one Physician at your facility may have had a patient with Ameloblasic carcinoma, and could maybe shed some light on potential treatment options?
Any assistance you may be able to provide, we would be ever so grateful!
Ilook forward to hearing from you!

Jennifer, our physicians have extensive experience treating many rare cancers. If you'd like to learn more, you can call 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment for more information. Thank you for your comment.
.

Diag. with adenoid cystic carcinoma in left submandibular gland? Is this unusual? Have had surgery and will be starting radiation.

Margaret, adenoid cystic carcinoma is considered a rare cancer. If you would like to learn more about it, we recommend you go to the website for the Adenoid Cystic Carcinoma Research Foundation at http://www.accrf.org/. If you'd like to make an appointment with a Memorial Sloan-Kettering doctor, you can call 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment for more information. Thank you for your comment.

My brother was just diagnosed with a benign inverted papilloma. They just removed this via endoscopic surgery. The Doctor is now recommending another surgery to remove bone from his face. The Doctor says it is good to do to lessen the recurrence rate. Is this a typical recommendation? Should my brother go for an additional (more invasive) surgery? Should he get a second opinion? Thank you!

Ericka, we are not able to answer individual medical questions on our blog. If your brother would like to speak with a doctor at Memorial Sloan-Kettering about obtaining treatment or a second opinion, one of you can call 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment for more information. Thank you for your comment.

This is great news. I am 6 months post-op and 1 month post-radiation. I had my tumor banked at MD Anderson. How can I get the genes sequenced?

Theresa, we are looking into this for you, and will get back to you as soon as we can with a response. Thanks for your comment.

10/11 ACC of parotid resected /peeled off my facial nerve without nerve damage, positive margins and perineural invasion. Neutron beam radiation in Seattle with Dr. Larimore and Parvathaneni. Now mets to all sections of my lungs too numerous to count and between CT on 12/10 and 1/7 all nodules have increased to double in size. Biopsy + for ACC lung mets; biopsy tissue does not have HER2.
Am trying to find what target therapy will work for this very aggressive form of ACC. I am completely symptom free, do aerobic exercise for 30 minutes and 30 minutes deep yoga breathing and feel fantastic. Any direction. I would like to see studies indicating stable disease versus response outcomes. Can you direct me.

Linda, we recommend that you reach out to the National Cancer Institute's Cancer Information Service at 800-4CANCER. You might also want to go to the National Institutes of Health's clinical trials database at www.clinicaltrials.gov to find studies in your area. Thank you for your comment.

I have to clarify my surgery date, it was in 2011, and the recent mets on CT are from 2013 Dec 10 and 2014 Jan 7. Hope that was not confusing. I have been in touch with the Adenoid Cystic Research Foundation.

I was diagnosed w/ACC 8/2011 had submandibular removed, had 7 wks of radiation. Came back 1 year later, had 2 more surgeries in 2012. Another tumor sprouted 3 months after these surgeries. Then went to see cancer specialist at Moffitt Cancer Ctr in Tampa. In Jan of 2013 had a facial dissection, and just had 1st MRI after this surgery, and I have another tumor at my jawline. Having my 5th surgery on 1/24/14 - I would like to see Dr. Chan when I come up to NYC this summer. Thank you

January, if you would like to make an appointment with a Memorial Sloan-Kettering physician, please call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. Thanks for your comment.

I will have to do that, when I know the dates I will be in NYC thanks

My sister was also diagnosed with ACC last year. She had seven weeks of radiation in Heidelberg, but could not have surgery. Now the tumor is back. We live in Europe. Is there any possibility that she could have such a targeted therapy by a specialist here or does you also treat persons from Europe? Thanks a lot!!!

Neyrinck, we are sorry to hear about your sister's diagnosis. To look for treatments in Europe that might be right for her, we recommend that you go to www.clinicaltrials.gov and search on her type of cancer and your country. This is a registry of clinical trials around the world maintained by the US National Institutes of Health. If she is interested in coming to MSK from Europe, or in arranging to have doctors at MSK review her records, she can contact our Bobst International Center at international@mskcc.org or go to http://www.mskcc.org/cancer-care/international-patients for more information. Thank you for your comment.

Add a Comment

We welcome your questions and comments. Because this is a public forum, please do not include contact information or other personal details. Also, keep in mind that while we can provide general information and resources, we cannot offer personal medical advice. To make an appointment with one of our experts, contact our Physician Referral Service at 800-525-2225 or online.
Your e-mail address is kept private and will not be shown publicly.

More information about formatting options