Mutational Signatures in Pediatric Cancer-from Etiology to Therapeutic Implications
Forum Chairs
Forum Description
The signatures of mutation in cancer genomes are markers of past mutagen exposure or intrinsic DNA repair defects. Recent studies in childhood cancer have shown that mutational signatures can uncover a tumor’s origin - including whether it arose due to inherited mutation – and point to therapeutic vulnerabilities. In this meeting, we will discuss the enormous potential utility for mutational signatures in childhood cancer, in predicting future outcomes and eligibility to clinical trials, mechanisms for therapy-induced drug resistance, as well as performing “reverse genetics” – understanding the tumor’s past evolutionary trajectory and possible etiology. Knowing that childhood cancers are unique, this meeting’s participants will propose mutational signatures approaches that have been adapted for these patients specifically. This will include focusing on thresholds for detecting underlying mutational signatures, such as mismatch repair and homologous recombination, as well as signatures involving structural rearrangements, which are frequent drivers of childhood cancer malignancy.
Forum Summary
The Forbeck Foundation hosted an in-person meeting at the Monterey Peninsula in Pacific Grove, California, which provided the perfect venue for focused discussion and collaborative brainstorming on the topic of mutational signatures in childhood cancer. The meeting was chaired by Stephen Chanock, MD of the National Cancer Institute, Jinghui Zhang, PhD of St Jude Children’s Research Hospital, and Adam Shlien, PhD of the Hospital for Sick Children. Three rising stars were invited as Forbeck Scholars: John Prensner, MD, PhD, Emre Kocakavuk, MD, and Andrew Hong, MD.
The two day meeting was organized into four main sessions: 1) Signature analysis - an art or science or both?; 2) Context of Signatures: what do they tell us?; 3) Signatures and Biology in Pediatric Cancer; and 4) When, where and how are signatures informative in pediatric oncology?
The discussions started by going back in time. The first set of talks focused on using signatures to define the early origins of childhood cancer, which can be many years before diagnosis. A particular emphasis was placed on the roots of secondary neoplasms amongst long-term survivors of pediatric cancer and therapy-related signatures in leukemia. The conversation then turned to understanding the ongoing evolution of childhood cancers, including the mutational impact of radiotherapy, which can both cause and help cure cancer.
We then turned our attention to intrinsic factors leading to mutation. Dysfunctional DNA repair caused by somatic or germline mutations, whether via the homologous recombination or mismatch repair pathways, was noted to be an important source of somatic mutagenesis in childhood cancers. While each creates unique repertoires of mutations, the participants discussed the challenges and opportunities in better defining these signatures. A particular emphasis was placed on the BRCAness signature because of its potential to guide therapy and the recognition that an update to COSMIC v.3 reference signatures may require a revision on BRCAness signature in pediatric cancer.
Finally, we heard of important progress and upcoming work using mutational signatures to improve the treatment of young people with osteosarcoma, neuroblastoma, high-grade glioma and other malignancies. Challenges on incorporating mutational signatures for patient enrollment were also discussed. Moving beyond the childhood years, the attendees discussed the long-term comorbidities associated with cancer treatment, focusing on the use of mutational signatures to measure the impact of chemotherapy in survivors.
The participants commented that this was one of the best meetings they had participated in. The quality of the science and discussion was extremely high, and there was a sense of a shared mission to work collaboratively to put these findings into practice.
Venue & Travel Information
800 Asilomar Avenue
Pacific Grove, CA 93950
Travel Forms
Travel forms are due 30 days prior to the start of the meeting to allow enough time to plan transportation.
To help reduce transportation costs, the Foundation tries to group travelers on shuttle vans rather than providing transportation for single travelers. The times below are not exclusive but represent times that we hope to have shuttles leave the airport.
The Monterey Regional Airport (MRY) is the preferred airport as it is only 20 minutes from the meeting location.
- Arrivals to MRY - Thursday around 1 PM, 3 PM and 5 PM
- Departures from the meeting venue - Sunday around 8 AM, 10 AM, and 12 PM
San Francisco International Airport (SFO) is 2 hours from the meeting location without traffic. The Foundation tries to prioritize International Flights and situations where flying into SFO is significantly cheaper than connecting to MRY. The times below are for guidance only, and depending on the volume of travelers, we may add an additional shuttle to and from the airport.
- Arrivals to SFO - Thursday around 3 PM
- Departures from the meeting venue - Sunday around 10 AM
Travel Policy
Please familiarize yourself with our policies and procedures for travel. We truly appreciate you taking the time to participate in this meeting. As you make your plans, please remember that we are a nonprofit organization dependent on donations and volunteers. We do NOT pay for upgrades, change fees, incurred costs resulting from a flight change, transportation to or from your local (home side) airport, meals or other incidentals.
- Travel Confirmation will be sent out within 1 week of the meeting. This will include a hotel confirmation number, if there is one, and airport transfer details. We have to wait until we receive almost everyone’s travel to book airport transfer. Due to frequent airline changes, we wait until the week of the meeting to send this out.
- Airport transfer is provided by Foundation staff, volunteers or arranged shuttle at specific times. If you opt to utilize Foundation airport transportation on your travel form, please be patient in receiving this information. We will send it to the week of the meeting.
- Speaker agenda is not sent out prior to the meeting. It will be provided upon arrival in the meeting packet. We do not tell people when they are speaking because we expect everyone to attend all sessions. Sessions are all day Friday and Saturday.
- REMINDER: We do not reimburse for home side airport transfer or incidentals while traveling. We will not honor miscellaneous receipts sent for these expenses.
- Spouses are welcome to come with you at their own cost but are not allowed to attend the meeting. Please no children.
What the Foundation Pays
Accommodations and meals are provided by the foundation during the meeting. Airfare will be covered only if booked through our travel agent. The Foundation will also cover airport transportation on the meeting side at the designated shuttle times. You can select not to utilize Foundation arranged transportation at your own expense when completing the travel form. Once your travel form is received your accommodations and airport transfer will be confirmed. Please let us know of any food allergies or other information we should be aware of on the travel forms.
- If you would like your airfare covered by the Foundation, you must book with our travel agent. Note we do not cover upgrades, changes, late bookings, etc.
- Flights must be booked at least 30 days prior to the meeting to confirm your accommodations and airport transfer.
- As a nonprofit we utilize volunteers and other methods to maximize our efforts (or our donor support) when making accommodations and arranging ground transportation. Ground transportation will be provided upon your arrival either by a foundation volunteer or arranged shuttle. You will be provided airport transportation information the week of the meeting. We do not reimburse for home side airport transfer or incidentals while traveling.
Abstracts
Abstracts are due 30 days prior to the start of the meeting to allow enough time to prepare the meeting book.
The abstracts should be only one or two paragraphs outlining the theme of your presentation and should reflect the objective and spirit of the meeting (see above). Abstracts will be circulated about one week before the meeting. The meeting organizer will start requesting them a month before the meeting.
Meeting Structure
The meeting structure has been developed over years of experience.
- Participants have approximately 45 minutes, depending on the number of participants, for their presentation and discussion. The presentation is meant as a conversation start and should last about twenty minutes briefly covering background information and areas that are new or need further input. This should be structured in such a way as to lead to a lively discussion. Participants are encouraged to interrupt to ask questions or start discussions.
- A MAXIMUM of 5 slide equivalents per presentation is allowed (Power point slides should not contain more than one graph or gel per slide and no more than 5 bullet points to stress the points being made by the presenter.) We appreciate cooperation with the spirit of this guideline. Handouts are welcome but should be distributed before sessions.
- Everyone is expected to actively participate in every session and discussions.
- The time spent at the meeting is relatively short, so please be familiar with papers received prior to the meeting.
- It is very important that you commit to all sessions of the 2 days of meetings.
Forbeck Scholars Participation
Scholars are selected for each Forbeck Forum. These are outstanding junior clinical or post-doctoral fellows selected based on the quality and relevance of science.
- Scholars present for 30-45 minutes, depending on the number of participants
- The same presentation rules apply for scholars
- After the Forum you are selected to attend, you will attend three years of Scholar Retreats held in Lake Geneva, WI. If you attend a Fall Forum, you will attend the Spring Retreat. If you attend a Spring Forum you will attend a Fall Retreat.
- Scholars are selected by the Foundation Scientific Advisory Board and peer reviewers selected from past Forbeck Scholars.
General Program
The outline below illustrates a typical program schedule. You will receive a complete schedule, including speaking times, the Thursday the meeting starts.
Frequently Asked Questions
Below are some of our most Frequently Asked Questions. If you have something new to ask, please feel free to contact us.
- Travel Confirmation will be sent out within 1 week of the meeting. This will include a hotel confirmation number, if there is one, and airport transfer details. We have to wait until we receive almost everyone’s travel to book airport transfer. Due to frequent airline changes, we wait until the week of the meeting to send this out.
- Airport transfer is provided by Foundation staff, volunteers or arranged shuttle at specific times. If you opt to utilize Foundation airport transportation on your travel form, please be patient in receiving this information. We will send it to the week of the meeting.
- Speaker agenda is not sent out prior to the meeting. It will be provided upon arrival in the meeting packet. We do not tell people when they are speaking because we expect everyone to attend all sessions. Sessions are all day Friday and Saturday.
- Frequently airport transfer is provided by volunteers. Please be patient on receiving this information. Airport transfer will be sent out prior to arrival.
- REMINDER: We do not reimburse for home side airport transfer or incidentals while traveling. We will not honor miscellaneous receipts sent for these expenses.