Genome-wide association study of germline copy number variations reveals an association with prostate cancer aggressiveness.

Prostate cancer is a major health burden, being the second most commonly diagnosed malignancy in men worldwide. Overtreatment represents a major problem in prostate cancer therapy, leading to significant long-term quality-of-life effects for patients and a broad socio-ecological burden. Biomarkers that could facilitate risk stratification of prostate cancer aggressiveness at the time of diagnosis may help to guide clinical treatment decisions and reduce overtreatment. Previous research on genetic variations in prostate cancer has shown that germline copy number variations as well as somatic copy number alterations are commonly present in cancer patients, altering a greater portion of the cancer genome than any other type of genetic variation. To investigate the effect of germline copy number variations on cancer aggressiveness we have compared genome-wide screening data from genomic DNA isolated from the blood of 120 patients with aggressive prostate cancer, 231 patients with non-aggressive prostate cancer and 87 controls with benign prostatic hyperplasia from the Prostate Cancer Study of Austria biobank using the Affymetrix SNP 6.0 array. We could show that patients with an aggressive form of prostate cancer had a higher frequency of copy number variations [mean count of copy number segments (CNS) = 12.9, median count of CNS = 9] compared to patients with non-aggressive prostate cancer (mean count of CNS = 10.4, median count of CNS = 8) or control patients diagnosed with benign prostatic hyperplasia (mean count of CNS = 9.3, median count of CNS = 8). In general, we observed that copy number gain is a rarer event, compared to copy number loss within all three patient groups. Furthermore, we could show a significant effect of copy number losses located on chromosomes 8, 9 and 10 on prostate cancer aggressiveness (P = 0.040, P = 0.037 and P = 0.005, respectively). Applying a cross-validation analysis yielded an area under the curve of 0.63. Our study reports promising findings suggesting that copy number losses might play an important role in the establishment of novel biomarkers to predict prostate cancer aggressiveness at the time of diagnosis. Such markers could be used to facilitate risk stratification to reduce overtreatment of prostate cancer patients.

Post-chemotherapy microscopic residual prostate rhabdomyosarcoma: long-term conservative follow-up.

In spite of advances in the treatment of childhood bladder and prostate rhabdomyosarcoma (RMS), the ability to detect minimal residual disease correlates imperfectly with the ultimate outcome. We report the long-term follow-up of a child with microscopic residual RMS after chemotherapy. The correct interpretation of the histologic findings spared the child unnecessary additional therapy and raises enigmatic questions about the biology of minimal residual disease.

Neurofibromatosis and associated neuroectodermal tumors: a congenital neurocristopathy.

The synchronous occurrence of neurofibromatosis and neuroblastoma has been labeled in the recent literature as a chance event. We report 2 cases of newborn infants with congenital neurofibromatosis and a similar midline pattern of multiple Schwann cell and neuroblastic tumors; other types of ectomesenchymal tumor differentiation are documented, along with supportive ultrastructural and immunohistochemical studies. The tumors may take an aggressive, fatal course despite maximal multimodality antitumor therapy. These 2 cases are reported, with additional literature review, to document a clinically recognizable neurocristopathy that links neuroblastic tumors and neurofibromatosis.