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A More Accurate Way to Predict Relapse Risk? data set [6,000 individuals from the United K ingdom] generated from genomic data." Dr. Turnbull and co-investigators from Germany, Sweden and the United States sought to re-examine the heri- tability of testicular cancer using the Swedish Population Registry data, and to use the combined population and genomic data to determine what percentage of testicular cancer's heri- tability they had accounted for in their ongoing research. Their conclusion: They have uncovered 25 percent of testicular cancer's genetic basis. The researchers published their fi ndings from the combined popula- tion-based and genomic analysis in Scientifi c Reports in September 2015. DELAYED MANIFESTATION The study found that approximately 50 percent of testicular cancer risk is inherited, a much higher heritability f ig ure t ha n t hat of ot her ca ncers. T he rea son cou ld be t he way t he cel lu la r foundation for testicu la r ca ncer for ms, beg inning in utero, according to Dr. Turnbull. " The biologica l hy pothesis is that the f irst oncogenic events leading t o t e s t ic u l a r c a nc er a r i se at t he feta l sta ge w it h t he conversion of t he nor ma l progen itor ger m cel ls i nto ca rci noma i n sit u cel ls," she says. " These cel ls sit quiet ly unti l adolescence, when they 're exposed to the hormona l surge a nd proliferate. After a f ive- to 15-year lag time, they become i nva sive a nd ma nifest a s testicular cancer. These are actua lly embr yona l tumors that then become manifest in early adulthood, and this could account for the higher propor- tion of genetic susceptibility to these tumors rather tha n environmenta l factors causing them." T h e a u t h o r s c o n c l u d e t h a t i d e nt i f y i n g a l l ge n e t i c v a r i a nt s a s soci at ed w it h t es t icu la r ca ncer c o u l d l e a d t o t h e d e v e l o p m e n t of p er s on a l i z e d r i s k s cr e en i n g s . T hey a re cont i nu i n g t hei r work t o i dent i f y c om mon a n d r a r e v a r i- a nt s u si n g genot y pi n g a nd exome s e q uenc i n g , r e s p e c t ive ly, i n t he hope of u n lock i n g more of t es t icu- la r ca ncer 's DNA-ba sed secret s . ■ CLINICIA NS SOON M AY be able to help men with a common type of testicular cancer — nonseminomatous germ cell tumor — make more informed decisions about managing the potential for recurrence. Currently, clinicians use the presence of vascular blood vessels in the tumor to assess the risk of relapse in men with stage 1 nonseminomatous germ cell tumor — an imprecise method that can lead to unnecessary che- motherapy, according to Professor Janet Shipley, Team Leader of Sarcoma Molecular Pathology and Interim Head of the Division of Molecular Pathology in the Divisions of Molecular Pathology and Cancer Therapeutics at the Institute of Cancer Research, London. "Patients with stage 1 nonseminomas face the diffi cult choice of being monitored in case their cancer returns or having chemotherapy straightaway, which they may not need," Shipley says. "Excess treatment may lead to problems later in life, including nerve damage, heart disease and increased risk of other cancers. Patients diag- nosed with stage 1 nonseminomatous testicular cancer have rates of recurrence of around 50 percent if there is evidence of blood vessels [vascular invasion] or 15 percent if blood vessels are absent. This indicates the current test based on assessing vascular invasion is not very accurate in predicting relapse." MORE PRECISE PREDICTORS Shipley and colleagues sought to create a more exact method of stratifying relapse risk based on factors known or suspected to be associated with recurrence, including vascular invasion, and molecular factors that infl uence tumor cell movement. Their fi ndings were published in Clinical Cancer Research in October 2015. The researchers tested the factors in 177 samples from participants in previous clinical trials who were being monitored for recurrence following surgical removal of their tumors. "The levels of a molecule called CXCL12, the percentage of the tumor with an appearance of cancer stem cells, and whether or not blood vessels were present in the tumor improved our ability to predict recurrence over only using the vascular invasion status," Shipley says. "Signifi cantly, this result was validated in an independent set of samples." The researchers assessed the tumor samples using the three factors and used a scoring system to stratify the patients into low-, moderate- and high-risk groups. About 94 percent of patients in the low-risk group were relapse- free after two years, compared with 65.9 percent in the moderate-risk group and 30 percent in the high-risk group. The researchers will now test the screening in larger cohorts. M D N E W S . C O M /// M D N E W S G R E AT E R K A N S A S ■ 2 016 1 9

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