
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.
Back to topQuiet 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.
Back to topFocus 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.
Back to topComments
Vickey Scaramella
May 28, 2013 • 11:47 PM
Memorial Sloan Kettering
May 29, 2013 • 10:25 AM
In reply to I have ACC and would like by Vickey Scaramella
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.
Linda Franklin
May 31, 2013 • 10:31 AM
Beverly Grace
May 31, 2013 • 2:57 PM
Memorial Sloan Kettering
May 31, 2013 • 9:12 PM
In reply to Any news on LMS? Please by Beverly Grace
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/clinic…. Please discuss your possible participation with your Memorial Sloan-Kettering doctor. Thank you for your comment!
Grace Pecora
May 31, 2013 • 8:20 PM
Memorial Sloan Kettering
Jun 1, 2013 • 9:35 AM
In reply to Similar to Linda above, my by Grace Pecora
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.
David
Jun 10, 2013 • 5:14 PM
Marsha
Jun 10, 2013 • 6:05 PM
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.
Bonnie Porthouse
Jun 14, 2013 • 5:39 PM
Memorial Sloan Kettering
Jun 14, 2013 • 8:23 PM
In reply to I am one year post op. by Bonnie Porthouse
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.
Anita Ransco
Jul 17, 2013 • 10:27 PM
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?
Memorial Sloan Kettering
Jul 18, 2013 • 7:54 AM
In reply to A very dear friend has been by Anita Ransco
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.
Ken Robinson
Jul 30, 2013 • 11:42 PM
Julia Ryan
Aug 8, 2013 • 11:36 PM
Susan Knott
Aug 22, 2013 • 9:41 AM
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.
E. Jennifer Elka (for John "Jay" Winter)
Sep 3, 2013 • 10:12 PM
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!
Memorial Sloan Kettering
Sep 4, 2013 • 8:30 AM
In reply to My domestic partner of 10 by E. Jennifer Elka (for John "Jay" Winter)
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.
.
Margaret
Oct 25, 2013 • 8:50 PM
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.
Ericka Hogan
Dec 20, 2013 • 1:52 PM
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!
Memorial Sloan Kettering
Dec 20, 2013 • 2:59 PM
In reply to My brother was just diagnosed by Ericka Hogan
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.
Theresa
Dec 26, 2013 • 9:57 AM
Linda Van Alstyne
Jan 15, 2014 • 9:20 PM
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.
Memorial Sloan Kettering
Jan 16, 2014 • 11:45 AM
In reply to 10/11 ACC of parotid resected by linda van alstyne
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.
Linda Van Alstyne
Jan 15, 2014 • 9:27 PM
January Hunter
Jan 17, 2014 • 9:21 AM
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
Memorial Sloan Kettering
Jan 17, 2014 • 9:33 AM
In reply to I was diagnosed w/ACC 8/2011 by January Hunter
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.
January Hunter
Jan 17, 2014 • 1:22 PM
Neyrinck
Jul 11, 2014 • 1:57 PM
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!!!
Memorial Sloan Kettering
Jul 11, 2014 • 2:14 PM
In reply to My sister was also diagnosed by Neyrinck
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 [email protected] or go to http://www.mskcc.org/cancer-care/international-patients for more information. Thank you for your comment.
Carol
Jul 28, 2014 • 5:25 PM
Dear Carol, thank you so much for reaching out to us. We cannot provide you with personal medical advice on our blog, but if you would like to make an appointment to see an MSK doctor, you can call 800-525-2225 during regular business hours. Here are more details for you on making an appointment: http://www.mskcc.org/cancer-care/appointment. We can provide you with general information about treatment at Memorial Sloan Kettering if you know what type of cancer you have. Thanks again for contacting us, and we wish you all the best.
Geraldine Gallagher
Sep 23, 2014 • 8:51 AM
My 40 year old daughter (single mom with a 6 year old child) had left side of thyroid with a very large 8 cm mass removed in July. It was discovered that she has Hurthle Cell Carcinomas with 4 sites of angio-invasion. The right side of thyroid was removed in August. The cells were present in the right side but were not cancerous. Since Hurthle cell has a slow uptake of iodine, I am worried that thyrogen & radioactive iodine therapy won't be enough to destroy any cells that might remain. It is unknown at this time if it has spread. What would be your suggestion.
Memorial Sloan Kettering
Sep 23, 2014 • 9:14 AM
In reply to My 40 year old daughter by Geraldine Gallagher
Geraldine, we are sorry to hear about your daughter’s diagnosis. Unfortunately, we are unable to answer specific medical questions on our blog. 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.
Geraldine Gallagher
Sep 23, 2014 • 8:53 AM
Randy B
Nov 15, 2016 • 12:48 AM
I am currently being treated with a clinical trial of Keytruda for ACC now in my lungs (City of Hope). It first presented in my throat, but surgery and radiation took care of this four+ years ago (USC). The jury is out on the success. We are also getting a second genomic study done - the first showed no markers. I'd be interested in the current status of the study noted in this article or another. Thank you. I am 55 years old, male, otherwise very healthy.
Memorial Sloan Kettering
Nov 16, 2016 • 1:34 PM
In reply to I am currently being treated… by Randy B
Dear Randy, we sent your comment to Dr. Chan, who replied, “ACC has relatively few targetable mutations so immunotherapy is a reasonable approach to try. There are some new trials based on genomic information like the BET inhibitors.” You may want to ask your doctor if any of these trials are available in your area. Thank you for your comment, and best wishes to you.
Joel
Jul 20, 2017 • 10:32 AM
Dear Joel, we’re sorry to hear about your diagnosis. If you would like to arrange for a consultation to speak with someone at MSK about treatment options, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment, and best wishes to you.
I have ACC and would like any updates you have and would like to be on an email list if possible??