Gene Mutation Linked to Aggressive Form of Sarcoma Affecting Children and Young Adults

Pictured: Marc Ladanyi

Molecular pathologist Marc Ladanyi

Researchers at Memorial Sloan Kettering have discovered a gene mutation that may explain why a subset of patients with rhabdomyosarcoma — a rare cancer that affects mainly children and young adults — have a particularly aggressive form of the disease that responds poorly to standard treatments such as chemotherapy.

The results, reported recently in Nature Genetics, could guide physicians in tailoring rhabdomyosarcoma treatments and could also lead to the development of new drugs for the disease.

What Is Rhabdomyosarcoma?

Rhabdomyosarcoma arises in cells that form skeletal muscle and usually affects children five or younger. Less commonly, it is diagnosed in older children and young adults. The condition is a type of soft tissue sarcoma, a group of more than 70 rare cancers that originate in soft tissues such as fat, muscles, nerves, and tendons.

“Because there are so many subtypes of soft tissue sarcoma, and each person’s disease differs in its behavior and genetic makeup, some of these cancers tend to be very difficult to diagnose and treat,” says molecular pathologist Marc Ladanyi. He led the study, which is part of an extensive MSK effort to determine the gene changes that drive distinct sarcoma subtypes.

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How the Study Was Done

The researchers analyzed 20 rhabdomyosarcoma tumors by whole-exome sequencing, a method of obtaining comprehensive blueprints of DNA changes in tumors by analyzing all parts of the genome that code for protein.  The tumor samples had been taken from patients with the two most common subtypes of the disease — embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma — who had been treated at MSK. The age of these patients varied from one to 25 years.

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A Striking Finding

As the researchers surveyed information about the thousands of genes in these tumors, one finding particularly grabbed their attention: Two of the 11 ERMS tumors analyzed had the exact same mutation in a gene called MYOD1, which had not previously been linked to the disease.

“Remarkably, research done more than two decades ago had shown that this mutation interferes with the development of skeletal muscle cells,” Dr. Ladanyi says. “Immature muscle cells that have the mutation proliferate uncontrollably instead of maturing into normal muscle cells.”

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An Aggressive ERMS Subtype

The researchers analyzed tumor samples from an additional 93 ERMS patients to specifically look for the MYOD1 alteration. Overall, it was present in almost one tumor out of ten. The prevalence of the mutation was higher among tumors in teenagers and young adults, and less frequent among small children and infants.

“We noticed that the teenagers and young adults whose tumors had the mutation did very poorly compared to others with ERMS,” Dr. Ladanyi says. “This finding is immediately helpful to pediatric oncologists because it gives them a new way to identify those patients who might need more intensive treatment.”

In addition, the researchers analyzed 25 alveolar rhabdomyosarcoma samples and did not detect the mutation in any of these tumors, suggesting that it occurs mainly in ERMS.  

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How the Research Moves Forward

In Dr. Ladanyi’s lab, researchers are now conducting large-scale screens of ERMS tumors that carry the MYOD1 mutation to find new therapies that could be especially effective against these difficult-to-treat cancers.

In the current study, the researchers noted that half of the tumors that had the MYOD1 mutation also had gene changes that affect a cellular process called the AKT pathway — an indication that ERMS tumors with the MYOD1 mutation might be sensitive to a family of drugs called PI3 kinase inhibitors.

“This gives us hope that patients with this subtype of the disease for whom standard treatments often fail potentially could benefit from targeted therapy in the future,” Dr. Ladanyi explains. “However, more research is needed to understand what types of drugs individual patients might benefit from.”

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This research was supported by a generous donation by Mortimer B. Zuckerman and by the National Institutes of Health under award numbers CA047179 and CA140146.


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This is great news but I'm curious about the latest on neuroblastoma. Seems as though nothing new since my sons passing in 2006. Would love to see some progress in that direction.

Our niece is one of those rare older patients with Rhabdomyosarcoma. We are so pleased and blessed that she is being treated at the premier cancer treatment in the world, MSK. Keep up the great work and cure this hideous disease!

any updates or new treatments for desmoplastic small round blue cell daughter is 12 and fighting this ugly cancer please any news or help

Dear Mischca, we are sorry to hear about your daughter’s diagnosis. We sent your inquiry to Dr. Paul Meyers, one of our pediatric oncologists, and he responded:

“Our research has indicated that desmoplastic small round cell tumor is very dependent on the VEG-F pathway. We have a clinical trial which uses chemotherapy in conjunction with bevacizumab, an inhibitor of the VEG-F pathway to achieve better control of this tumor. When we are able to achieve a significant tumor response, we have an investigational study which we hope will treat the residual disease. We administer a monoclonal-antibody conjugated with a radio-isotope into the peritoneal cavity to deliver radiation directly to tumor cells while minimizing the radiation exposure of healthy organs.”

If you have additional questions and would like to make an appointment to see if your daughter is a candidate for this clinical trial or other treatment options at Memorial Sloan Kettering, please call our Department of Pediatrics at 212-639-5954. Thank you for reaching out to us.

Can you tell me if there are any updates on treatment for relapsed osteogenic sarcoma since my son's passing in 2007?

Dear Kathy, we are very sorry for your loss. We sent your inquiry to Dr. Paul Meyers, one of our pediatric oncologists, and he responded:

“Memorial Sloan-Kettering Cancer Center offers several new approaches to patients with osteosarcoma that has recurred after prior treatment:
1. For patients whose pulmonary metastases can be completely resected, we offer a clinical trial of cisplatin encapsulated in liposomes (microscopic particles) by inhalation. This approach delivers a high concentration of chemotherapy to the lungs with almost no chemotherapy to the remainder of the body, avoiding the side effects usually seen with cisplatin.
2. We have a clinical trial of monoclonal antibody 3F8 which recognizes the GD2 antigen. This antibody has significantly improved the outcome for a different childhood cancer called neuroblastoma, which also expresses the GD2 antigen. We hope to achieve similar improvements in osteosarcoma.
3. We have a clinical trial of a new drug, cabazitaxel, which showed promise in laboratory investigations against osteosarcoma.”

Thank you for your comment.

My son is a 48yo physician with recurrent Ewing's sarcoma which originated in his acetabular roof. He was treated at Mt.Sinai with initial good response, but relapsed after several months, underwent radical pelvis resection, but again has recurrent pelvic tumor mass and pulmonary metastatic disease. He is now being treated with tapotecan and cytoxan which has limited progression but not decrease in tumor. Might his disease warrant consideration for evaluation in the manner you have applied to rhabdomyosarcoma? Is it possible PI3 kinase inhibitors offer any hope?

Dear Barry, we are sorry to hear about your son. We are unable to answer personal medical questions like this on our blog. If he would like to make an appointment for a consultation with one of our specialists to discuss possible treatment options, please ask him to call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

We love and support MSKCC. You are changing the world of cancer everyday. You are giving hope to sarcoma patients.

I am wondering about any new research regarding Leiomyosarcoma. I hold my breathe everyday waiting to hear some good news. Any light ?

Dear Jody, thank you for your kind words.

We are at the forefront of research on uterine leiomyosarcoma. Here is a link that outlines some findings about our research in gynecologic cancers, including leiomyosarcoma (read the first couple of bullets under chemotherapy):

We also currently have a Phase III clinical trial open for women with high-grade uterine leiomyosarcoma that may be of interest:

If you would like to learn more about it, please call the number offered in the trial description.

Thank you for your comment.

Any new developments in regard to cardiac angiosarcoma or ped. angiosarcoma in general. My 15 yr son died in March 2011 from re-lapse after a tumor in his heart had spread to his arm, hip and later his lungs. He had an excellent intial reaction to chemo and removal of tumor in his heart and arm but the hip tumor spread to his lungs 18 mos later.

Although this research is too late to save my daughter, I'm thankful there is progression in finding a better treatment for ERMS. For my daughter, the standard treatment didn't have much affect on the cancer.
Thank you for the work you do.

This is new and interesting data.

Thank you for working on ERMS. The four year anniversary of the death of my daughter from the spread from left leg (even after amputation and 54 weeks of 7 different chemo drugs) to her heart is just around the corner. Knowing someone cares enough to research this rare monster helps those who have lost a love one. Thank you

I have a sis in malaysia who has sarcoma.She had her right leg amputated 2yrs ago.she goes every 3mths for checkup.Now she has pain again in her right has been amputed right up to her hip.what is going to happen now.she is not getting chemo or radiotheraphy.she is 76yrs old.she is been to the unversity hospital in petaling jaya kuala lumpur malaysia.thank you.

my son has relapsed ERMS last week. i wonder if MSKCC offers immunotherapy for pediatric with relapsed ERMS.

thank you,

Dear Eila, we offer several innovative treatment strategies to help children whose disease has relapsed. At this time, immunotherapy is not one of them. But we do hope you’ll give our pediatrics team a call to learn more about options that might be right for your son. The number is 212-639-5954. You can read more about the treatments we offer for rhabdomyosarcoma here: Thanks so much for reaching out to us, and we wish you are your family all the best.

Our son-in-law was diagnosed with Stage 4 Pleomorphic Rhabdomyosarcoma three days after his 29th birthday. He did a 5 day chemo treatment 2 weeks after being diagnosed and was admitted to the Mayo clinic in MN on July 2, 2015, and had open heart surgery on July 4th. He passed away on July 13, 2015, 41 days after being diagnosed.

Bill, we are very sorry for your family’s loss.


My 5 year old son is diagnosed with embryonal Middle ear rhabdomyocarcoma in June 2015.
Currently he is undergoing treatment as per IRS V Protocol POG D9803 for intermediate risk rhabdomyosarcoma. He is undergoing VAC Chemotherapy and has completed 28 sittings of Radiation too. We are at Week 24 of Treatment Plan. The Volume of Tumor size is shrinked by 60 % since the diagnosis. We would like to have a second opinion.
The questions particularly we have :
1. Is there a way to find out whether the Remaining residual Tumor is active/ inactive ?
2. Would need an opinion on the treatment plan.

My 15 year old son was diagnosed with embrynol rhabdomyosarcoma in Sept. 2015. He has a 5 1/2 cm tumor behind his left cheek. He is in week 25 of a 42 week treatment plan. After 3 or 4 rounds of VAC the doctors said he had a poor response so far, so they added an extra week of proton radiation to his treatment. My son seems to fit all the criteria for the gene mutation MYOD1. I would like to talk to someone about this, please, before going to Sloan Kettering, as I live in Cleveland, Ohio.
Thank you

My 21 year old daughter Olivia was diagnosed with embryonal rhabdomyosarcoma last year. After a year of 4 different types of chemo and 2 types of radiation (with extensive nerve damage in her feet), this cancer has mestastasized from her jaw down to her lower back. The doctors want to treat her again with chemo which I'm convinced will kill her this time around. My family and I have done extensive research on the subject since her new diagnosis of being stage 4. We have completely changed her diet and are trying supplements but we need to find out what else can be done instead of chemo. She has agreed to additional chemo because the oncologist scared her into it and she feels stuck. Has anybody survived this type of cancer stage 4? I read that chemo is not effective at all (in terms of curing). in this type of stage 4 cancer. What if she just had radiation alone? Or an immuno-therapy? But we were told she HAD to have chemo and radiation first before such a therapy. Online we read the more chemo, the less immunity will be left for the body to respond to ANY therapy or treatment...
Please help.
Thank you.

Dear Fatimah, we are sorry to hear about your daughter’s diagnosis and everything she’s been through. If you would like to schedule an appointment with one of our specialists to discuss possible next steps in her care, please contact our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

My brother, Kevin Pirelli, was an Intra Abdominal Desmoplastic Small Round Cell Tumor patient at Montefiore Hospital in the Bronx from September 1994 until his death in February 1996. He was 23 at diagnosis and just 24 at death. I see that genetic markers have been noted in the tumor studies. Has any research indicated that this type of tumor could be genetically transmitted. I have an 18 year old son and 16 year old daughter and am wondering if there is any type of testing we should have done.
Thank you,
Karen Appelbaum

Dear Karen, we are very sorry for your loss. If your family has a history of cancer, you may want to speak with a genetic counselor about your family history and what the risks to other family members, including your children, may be. If you’d like to consult with MSK’s Clinical Genetics Service, you can call 646-888-4050 or go to… for more information. Thank you for your comment, and best wishes to you.

Any breakthroughs on Rhabdomyosarcoma with Myod1? Does Sloan Kettering work with doctors around the world comparing clinical studies results on this rare condition?? Sloan is amazing, if anyone will find a cure for this horrific disease, I have to believe it will be Sloan. Please let me know if they have new drugs to treat this rare condition in an 18 year old male.

Dear Noell, MSK does have a research program in rhabdomyosarcoma and members of our team are active in the international research community. If you or someone you know would like to come to MSK to learn about treatment, including the possibility of participating in a clinical trial, the number to call is 800-525-2225. You can go to for more information on making an appointment. Thank you for your comment, and best wishes to you.