Medical Biophysics Graduate Student Association


Updates, opinion pieces, and news related to the department

Posts in Research
Top 30 Radiology Journals and Publications

Blogger Rachel Davis over at* has compiled a list of the top 30 radiology journals and publications. Even if your imaging project is not yet at the clinical stage, it is worthwhile to read up on the latest developments in clinical radiology and treatments so that we can strive to improve on the current medical technology through our research.

* A website dedicated to providing students with the information and tools they need to pursue a degree in radiology.

Check out her full article

Read More
Blog, ResearchGuest Blogger
Published!: Genetic screening enables personalized surveillance in Li-Fraumeni syndrome patients and significantly increases overall survival

By Diana Merino Each month we will review/feature an article published by one of our very own MBP students in the biology and/or physics stream.

This article features the publication "Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study" by Villani et al., Lancet Oncol. 2011 Jun; 12(6): 559-67. (PMID: 21601526) [Link to Paper]

Click! That’s all it takes to get your genome sequenced nowadays. But how would you benefit from knowing the genetic code that determines the most infinitesimal details of your being? What could you do with this information?

Imagine you sequence your genome and an underlying disease predisposition is uncovered in between your millions of T’s, C’s, A’s, and G’s...what would you do now? Would you benefit from subjecting yourself to constant tests and medical examinations with the hope of preventing disease?

These are perhaps some of the questions that individuals with Li-Fraumeni Syndrome (LFS) might have asked themselves at one point or another. LFS is a cancer predisposition syndrome in which patients have increased incidence for soft tissue sarcomas, osteosarcomas, brain tumors, adrenocortical carcinoma, leukemia and premenopausal breast cancer. About 70-83% of patients carry a germline mutation (a mutation found in every single cell) in the tumor suppressor gene TP53, which increases their lifetime risk of cancer to as high as 73% in males, and 93% in females. Although LFS patients would greatly benefit from a comprehensive surveillance protocol, no strict guidelines have been implemented to date, mostly due to the complexity of this syndrome as exemplified by the diverse range of tumors and variability of age at onset.

The latest Malkin lab publication examines the benefit of a comprehensive biochemical and imaging surveillance protocol in LFS families carrying mutations in TP53.

Dr. Anita Villani and colleagues identified 33 TP53 mutation carriers from 8 LFS families through a multi-institutional effort between the Hospital for Sick Children in Toronto, the Children’s Hospital of Los Angeles, and the Huntsman Cancer Institute at the University of Utah in Salt Lake City. 18 out of the 33 carriers decided to undergo clinical surveillance, which included various biochemical and imaging tests, such as blood tests, urinalysis, MRI and ultrasound scans. This surveillance strategy is specific for each cancer type associated with LFS and varied between children and adult patients due to the different frequency of diagnoses observed in each age category. For this analysis, the primary and secondary outcome measures were the detection of new cancers and overall survival, respectively.

The findings of this study were quite striking. In the surveillance group, 10 asymptomatic tumors were detected in 7 patients. These tumors included small, high-grade tumors and low-grade or premalignant tumors. All seven patients (100%) were alive after a median follow-up time of 24 months. On the other hand, 12 symptomatic tumors presented in 10 patients in the non-surveillance group. These tumors were mostly high-grade, high-stage tumors. Only 2 out of the 10 patients (20%) survived until the end of follow-up (p=0.0417). Overall survival analysis revealed that TP53 mutation carriers with LFS in the surveillance group had a 3-year overall survival of 100%, while those in the non-surveillance group had a 3-year overall survival of only 21% (p=0.0155).

The authors note that the surveillance protocol enabled the detection of smaller, pre-symptomatic malignancies that were managed before progression and metastasis. In most cases, the early detection of these malignancies prevented the use of systemic or radiation treatment and favouring the use of definitive localized treatments, which reduced the side-effects and the health burden that commonly used cancer therapies inflict on patients.

It is also important to note that part of the success of the surveillance strategy tested is adherence to follow-up appointments. The article addresses this by suggesting that adherence in patients with surveillance methods could be improved by continuous attention and engagement of a multidisciplinary team of specialists.

In patients with cancer susceptibility syndromes, the possibility of burnout is quite high due to lifetime surveillance. As such, it is crucial to implement surveillance protocols that address this issue and institute initiatives that decrease the risk of burnout through accountability systems.

In a day and age in which access to our genetic code is as simple as a cheek swab and a credit card payment, it is crucial to have the proper insight as to how this knowledge can be used for our benefit. This article demonstrates that personalized surveillance protocols, which are designed taking into consideration each individual’s genetic susceptibilities, are extremely effective at detecting early tumors and improving overall survival. In patients with LFS, the implementation of genetic testing and personalized screening strategies is necessary as it will help patients lead longer lives, increase quality of life through early tumor detection and avoidance of side effects associated to systemic treatments, and enable them to make informed lifestyle decisions.

Read More
Academic, ResearchMBPGSA
Published!: Responding to androgens? You need to deubiquitylate the histone variant H2A.Z

By Alison Aiken This post highlights the work of Ryan Draker from Dr. Peter Cheung’s lab, published earlier this year in Nucleic Acids Research (PMID: 21245042) [Link to Paper].

In order for DNA to fit into cells, it gets coiled around octamers of small, positively charged proteins: the histones. Two each of histones H2A, H2B, H3 and H4 form the core of the nucleosome, around which DNA is coiled. Variant histones, which can differ significantly from core histones in their amino acid composition, can replace core histones in the nucleosome and are normally deposited in specific regions. A variant of H2A, H2A.Z, has been implicated in several cellular processes, including the regulation of transcription. Interestingly, H2A.Z can have either a positive or negative influence on gene transcription. This histone variant can be post-translationally modified by either acetylation or mono-ubiquitylation. Previous work by the Cheung lab has shown that H2A.Z is ubiquitylated by Ring1b, an E3 ligase that is part of the Polycomb Repressive Complex 1, and that mono-ubiquitylated H2A.Z is associated with transcriptionally inactive chromatin. The authors hypothesize, therefore, that the deubiquitylase(s) for H2A.Z would play an important role in the activation of transcription.

Read More