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Purpose:Monoallelic germ-line deleterious mutations of PALB2 (partner and localizer of BRCA2) are associated with breast cancer risk and have been found in several populations, with carrier frequencies of ∼1-2%. Initially, these mutations were considered to have moderate penetrance, but accumulating evidence now indicates that they are associated with much higher risk.Methods:In this study, we sequenced the PALB2 coding regions unlinked to BRCA (breast cancer) genes in 575 probands from Italian breast cancer families recruited in Milan.Results:We found 12 carriers (2.1%) of deleterious mutations, and none of the mutations was found in 784 controls collected in Milan. One of these mutations, the c.1027C>T (p.Gln343X), was found to be recurrent in the province of Bergamo in northern Italy, being detected in 6/113 (5.3%) familial breast cancer cases and 2/477 (0.4%) controls recruited in this area (Fisher's exact test: P < 0.01).Conclusions:Our data provide confirmatory findings that, in the Italian population also, deleterious mutations of PALB2 are relatively frequent predisposing factors for breast cancer and may be associated with high risk of the disease.Genet Med 16 9, 688-694.

CD34+ peripheral blood hematopoietic stem cells (HSC) are usually collected following mobilization therapy accomplished by using growth factors (GF) such as rHuG-CSF or rHuGM-CSF with or without chemotherapy. A target dose of yielded CD34+ is usually prescribed by the attending physician depending on different protocols, which may include single or double transplantation. HSC collection usually is performed when at least 20 CD34+ HSC/microL are detected by means of flow cytometry. A cumulative dose of at least 2 x 10(6)/Kg/bw CD34+ HSC has been considered as the threshold to allow a prompt and persistent hematopoietic recovery. Unfortunately, this goal is not achieved by the totality of patients undergoing mobilization regimen. In fact, 5-46% of patients who underwent mobilization therapy fail HSC collection due to very low peripheral blood HSC CD34+ count. Patients' characteristics, including age, sex, stage of the underlying disease (complete or partial remission), diagnosis, previously administered radio/chemotherapy regimens, time-lapse from last chemotherapy before mobilization and mobilization schedule (including dose of GF) were considered as possibly predictive of poor or failed mobilization. We performed a retrospective analysis in 2177 patients from three large Italian academic institutions to assess the incidence of poor mobilizers within our patients' series. Therefore, a patient who fails a first mobilization (and when an HLA-compatible related on unrelated donor is not available) could undergo a second attempt either with different mobilization schedule or by using different GF, such as stem cell factor, growth hormone (GH), or more recently newly introduced drugs such as AMD3100, alone or in combination with rHuG- or -rHuGM-CSF. Thus, we investigated the fate of those who failed a first mobilization and subsequently underwent a second attempt or alternative therapeutic approaches.