An international team, led by researchers at the University of California San Diego School of Medicine, has developed and validated a genetic tool for predicting age of onset of aggressive prostate cancer, a disease that kills more than 26,000 American men annually.
The tool may potentially be used to help guide decisions about who to screen for prostate cancer and at what age.
Currently, detection of prostate cancer relies primarily upon the prostate-specific antigen (PSA) screening blood test. But PSA testing is not very good as a screening tool. While it reduces deaths from prostate cancer, indiscriminate PSA screening also produces false positive results and encourages over-detection of non-aggressive, slow-growing tumours.
“The existing PSA test is useful, but it is not precise enough to be used indiscriminately on all men,” said the study’s first author, Tyler M. Seibert, MD, PhD, chief resident physician in the Department of Radiation Medicine and Applied Sciences at UC San Diego School of Medicine. “As a result, it may prompt medical interventions like biopsy, surgery or radiotherapy that might not be necessary.”
Seibert, senior author Anders Dale, PhD, professor and co-director of the Center for Translational Imaging and Precision Medicine at UC San Diego School of Medicine, and colleagues in Europe, Australia and the United States, used genome-wide association studies (GWAS) to determine whether a man’s genetic predisposition to developing prostate cancer could be used to predict his risk of developing the aggressive and lethal form of the disease.
GWAS search individual genomes for small variations, called single-nucleotide polymorphisms (SNPs), that occur more frequently in people with a particular disease than in people without the disease. Hundreds or thousands of SNPs can be evaluated at the same time in large groups of people. In this case, researchers used data from over 200,000 SNPs from 31,747 men of European ancestry participating in the ongoing international PRACTICAL consortium project.
Using a method developed at UC San Diego, the researchers combined information from GWAS and epidemiological surveys to assess quantification for genetic risk at age of disease onset. “Polygenic Hazard Score methodology is specialized in finding age-dependent genetic risks and has already been proven to be very useful in predicting age of onset for Alzheimer’s disease”, said study co-author Chun Chieh Fan, MD, PhD, in the Department of Cognitive Science at UC San Diego.
“The polygenic hazard score is very versatile and can be applied to many age-related diseases,” said Fan. “In this case, the polygenic hazard score of prostate cancer captures the age variations of aggressive prostate cancer.”
Genotype, prostate cancer status and age were analysed to select SNPs associated with prostate cancer diagnosis. Then the data was incorporated into the polygenic hazard score, which involves survival analysis to estimate SNPs’ effects on age at diagnosis of aggressive prostate cancer. The results led to a polygenic hazard score for prostate cancer that can estimate individual genetic risk. This score was then tested against an independent dataset, from the recent UK ProtecT trial, for validation.  
“The polygenic hazard score was calculated from 54 SNPs and proved to be a highly significant predictor of age at diagnosis of aggressive prostate cancer,” said Seibert. “When men in the ProtecT dataset with a high polygenic hazard score were compared to those with average PHS, their risk of aggressive prostate cancer was at least 2.9 times greater.”
“And when we account statistically for the effect of the GWAS having disproportionately high numbers of men with disease compared to the general population, we estimate that the risk defined by the polygenic hazard score is 4.6 times greater.”
The study authors note that an individual’s genotype does not change with age, so the polygenic hazard score can be calculated at any time and used as a tool for men deciding whether and when to undergo screening for prostate cancer. This is especially critical for men at risk of developing prostate cancer at a very young age, before standard guidelines recommend consideration of screening.
University of California – San Diegoucsdnews.ucsd.edu/pressrelease/new_polygenic_hazard_score_predicts_when_men_develop_prostate_cancer

More than 100 industry experts to highlight the latest medical laboratory and diagnostics trends and innovation
The 5^th edition of MEDLAB Asia Pacific Exhibition & Congress, leading B2B business and educational platform in the field of laboratory and diagnostics for the Asia Pacific region, will offer visitors the opportunity to attend a series of scientific conferences that will cover advancement in science, technology and application of various laboratory techniques to strengthen cooperation between lab and clinic interface.
Supported by The Academy of Medicine, Singapore and accredited by Singapore Medical Council, the 15 CME-certified conferences will empower delegates with the knowledge and skills to guarantee the fastest, safest and most accurate laboratory results in improving patient service and care.
During the three-day congress, which takes place from 2 – 4 April 2018 at Suntec Singapore Convention & Exhibition Centre in Singapore, a variety of carefully-designed sessions, panel discussions, demonstrations and interactive activities will enable delegates to network and share best practices with more than 100 regional and international experts who are champions of laboratory medicine in the Asia Pacific.
The congress will host 11 dedicated laboratory tracks: Laboratory Management, ­Clinical Chemistry, Haematology & Blood Transfusion, Infectious Diseases, Point of Care Testing, Cytology, Molecular Diagnostics, Laboratory Informatics, Cardiac Markers, ­ Lab Testing: Obs Gyne & Women’s Health and Lab Testing & Management: Diabetes.
During these sessions, delegates will able schooled in a wide variety of key topics including the role of the laboratory director, 4^th generation sequencing, updates in assays to improve skills in test accuracy, digital pathology, and the evaluation of current and future biomarkers, to name a few.
Due to the expanding role of laboratory medicine, the meeting is combined with other clinical specialties that will underscore the overarching influence of the laboratory in medical decision-making and treatment. New conferences in the MEDLAB Asia Pacific Congress portfolio are: Obs Gyne & Women’s Health, Gynae-Oncology, Diabetes Management and Antimicrobial Resistance.
“The advent of groundbreaking diagnostic solutions is gaining pace across the region. By introducing new medical tracks from key specialties that interact with the laboratory, the 2018 MEDLAB Asia Pacific Congress will provide the latest evidence-based research into diagnosis and treatment as well as enhance cooperation between laboratory professionals and clinicians to enable the best possible patient outcomes.” said Rejoy Penacerrada, Senior Conference Producer, MEDLAB Asia.
MEDLAB Asia Pacific 2018  is supported by a large number of key healthcare federations and associations across the region including The Royal College of Pathologists of Australasia, Singapore Society of Pathology, College of Pathologists, Academy of Medicine of Malaysia, Indonesian Association of Clinical Pathologist and Laboratory Medicine, Singapore Society of Haematology, College of American Pathologists, Philippine Society of Pathologists, Inc., Philippine Society of Biochemistry and Molecular Biology, Philippine Society of Microbiology, Indonesian Association of Clinical Chemistry, Society of Infectious Disease Singapore, and Society of Cytology Singapore and Diabetes Singapore.
Held alongside the congress is the MEDLAB Asia Pacific exhibition – a platform for leading companies from across the globe to showcase current technologies and innovations in the field of laboratory and diagnostics to an expected 4,000 visitors.
MEDLAB Asia Pacific is also co-located with Asia Health, a trade exhibition for medical equipment, products, services and technologies hosting more than 250 international companies and bringing together the world of medical laboratory and healthcare under one roof.
Registration for the MEDLAB Asia Pacific Congress is now open via www.medlabasia.com.

Bone marrow biopsies are the gold standard for diagnosing and monitoring the progression of multiple myeloma, but these procedures are far too invasive to perform at every patient visit. Scientists from the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard, however, have shown that two ways to measure multiple myeloma DNA in blood samples provide highly detailed sets of genetic information that agree well not just with each other but with results from bone marrow tests.
“Until now, we haven’t had a good way to measure how multiple myeloma cell populations evolve from precursor stages to diagnosed disease, and then respond to treatments, says Irene Ghobrial, MD, a Dana-Farber medical oncologist. “This is where blood biopsies can make a huge difference—extending our understanding of multiple myeloma, and really giving us a timeline of how the disease progresses and responds to therapy.”
The collaborative research examined blood biopsies that gathered multiple myeloma tumour DNA from two sources. One is circulating free DNA (cfDNA), scraps of DNA released into the bloodstream by dying cells. The other is circulating tumour cells (CTCs)—myeloma cells themselves.
“Our discovery that cfDNA and CTC analyses agree with each other at the comprehensive level is an important finding, because this means that routine genetic profiling of patient tumours from blood would be feasible,” says Ghobrial, co-senior author on a paper reporting the work in Nature Communications.
The blood biopsy analyses followed a two-step sequencing approach, says Viktor Adalsteinsson, PhD, group leader of the Blood Biopsy Team at the Broad Institute and co-senior author on the paper. The first step, developed by his team and called “ultra-low pass” whole genome sequencing, was a cost-effective method to identify blood samples with tumour DNA fraction of at least 5-10%, allowing more comprehensive genetic analysis. In the second step, the researchers performed whole exome sequencing (analysing the protein-coding regions of the genome) on those samples.
The investigators examined cfDNA from 107 patients and CTCs from 56 patients. The scientists then matched up cfDNA with bone marrow data from nine patients, and compared all three forms of biopsy in four additional patients. Overall, the gene profiles overlapped closely—demonstrating about 99% agreement between liquid and bone marrow biopsies for tumour gene mutations, for instance.
Such high levels of agreement suggest that the two forms of liquid biopsy might be used interchangeably to track patients with multiple myeloma, the researchers say, and employing both techniques might further increase the chances of understanding the disease in each patient.

Dana-Farber Institutewww.dana-farber.org/newsroom/news-releases/2018/in-multiple-myeloma–different-types-of-blood-biopsies-match-up-well-with-bone-marrow-tests/

The facts about prostate cancer can be confusing. It’s the third most common cancer type among Americans –161,000 men will be diagnosed this year, the National Cancer Institute estimates. Yet according to the NCI, 98.6% will be alive in 5 years.
While it’s often not lethal, prostate cancer still kills lots of men –21,000 this year–because it’s so common. Many of its victims have metastatic disease at the time of diagnosis–their cancer has already spread. Can we catch potentially lethal cancers earlier to save some of these men?
This week, a team at Cold Spring Harbor Laboratory (CSHL) published encouraging results of a pilot study testing a new way of pinpointing the minority who have aggressive disease at the time of diagnosis–a fact that usually determines whether they will have surgery or not. Current procedure calls for a predictive diagnostic biopsy, in which a needle is inserted into the organ at various locations, sometimes guided by MRI and ultrasound.
The new method, which is proposed as a way of augmenting pre-surgical biopsy results, not replacing them, uses advanced genomic tools to analyse what doctors call “biopsy cores.” In standard diagnostic biopsies, pathologists examine the tissue collected in these cores, usually a dozen, and assign an overall grade called a Gleason score, based on changes in glandular architecture. A score of 6 or lower is usually interpreted to mean a cancer is slow-growing or “indolent.” Yet some men with borderline Gleason scores undergo surgery and are found to have aggressive cancers. Other times, men with high Gleason scores are found to have indolent cancers upon surgery.
The newly tested method, devised by CSHL Professor Michael Wigler and Associate Professor Alexander Krasnitz, draws the raw material for further analysis from the standard pre-surgical biopsy. The team sequences the genomes of several hundred single cells sampled from each patient’s diagnostic biopsy cores. They search for certain patterns—for the presence of DNA disturbances called copy-number variations (CNVs). Using computational methods to compare CNV patterns, the team looks for cells whose CNV profiles harbour the same irregularities. This is a sign of clonality. Cancerous tumours are composed of clonal cells—genetically aberrant cells that derive from a single wayward ancestor.
The CSHL method assigns a number to each set of biopsy cores, based on how many of the cores contain clonal cells, how many clonal cells each contains, and how far such cells have dispersed within the prostate. In tests on 8 patients based on collaborations with NYU and Cornell University medical centres, the CSHL testing method yielded assessments of tumours that more closely matched the verdict of post-surgical pathological analysis (which reveal actual pathology) than the corresponding pre-surgical predictive biopsies, according to first author Joan Alexander, M.D.
“This is important because treatment decisions in such cases depend on the pre-surgical biopsy, not the surgical specimen,” Krasnitz comments. “We think single-cell analysis could potentially augment traditional biopsy-core histopathology, significantly improving risk assessment and informing treatment decisions, especially in borderline cases.”
Cold Spring Harbor Laboratory
www.cshl.edu/new-method-determine-surgery-prostate-tumors-pose-lethal-threat/