BCR/ABL fluorescent in situ hybridization study of chronic myeloid leukemia (CML) and Philadelphia+(Ph+) acute lymphoid leukemia (ALL) indicated that approximately 9% of patients exhibited an atypical hybridization pattern consistent with a submicroscopic deletion of the 5′ region ofABL and the 3′ region of the BCR genes on the 9q+ chromosome. The CML patients with deletions had a shorter survival time and a high relapse rate following bone marrow transplant. Since deletions are associated with both Ph+CML and ALL, it seemed probable that other leukemia-associated genomic rearrangements may also have submicroscopic deletions. This hypothesis was confirmed by the detection of deletions of the 3′ regions of theCBFB and the MLL genes in AML M4 patients with inv(16) and in patients with ALL and AML associated withMLL gene translocations, respectively. In contrast, analysis of the AML M3 group of patients and AML M2 showed that similar large deletions were not frequently associated with the t(15;17) or t(8;21) translocations. Analysis of sequence data from each of the breakpoint regions suggested that large submicroscopic deletions occur in regions with a high overall density of Alu sequence repeats. These findings are the first to show that the process of deletion formation is not disease specific in leukemia and also implicate that the presence of repetitive DNA in the vicinity of breakpoint regions may facilitate the generation of submicroscopic deletions. Such deletions could lead to the loss of one or more genes, and the associated haploinsufficiency may result in the observed differences in clinical behavior.

Breast cancer brain metastases (BCBM) develop in about 20–30% of breast cancer (BC) patients. BCBM are associated with dismal prognosis not at least due to lack of valuable molecular therapeutic targets. The aim of the study was to identify new molecular biomarkers and targets in BCBM by using complementary state-of-the-art techniques. We compared array expression profiles of three BCBM with 16 non-brain metastatic BC and 16 primary brain tumors (prBT) using a false discovery rate (FDR) p < 0.05 and fold change (FC) > 2. Biofunctional analysis was conducted on the differentially expressed probe sets. High-density arrays were employed to detect copy number variations (CNVs) and whole exome sequencing (WES) with paired-end reads of 150 bp was utilized to detect gene mutations in the three BCBM. The top 370 probe sets that were differentially expressed between BCBM and both BC and prBT were in the majority comparably overexpressed in BCBM and included, e.g. the coding genes BCL3, BNIP3, BNIP3P1, BRIP1, CASP14, CDC25A, DMBT1, IDH2, E2F1, MYCN, RAD51, RAD54L, and VDR. A number of small nucleolar RNAs (snoRNAs) were comparably overexpressed in BCBM and included SNORA1, SNORA2A, SNORA9, SNORA10, SNORA22, SNORA24, SNORA30, SNORA37, SNORA38, SNORA52, SNORA71A, SNORA71B, SNORA71C, SNORD13P2, SNORD15A, SNORD34, SNORD35A, SNORD41, SNORD53, and SCARNA22. The top canonical pathway was entitled, role of BRCA1 in DNA damage response. Network analysis revealed key nodes as Akt, ERK1/2, NFkB, and Ras in a predicted activation stage. Downregulated genes in a data set that was shared between BCBM and prBT comprised, e.g. BC cell line invasion markers JUN, MMP3, TFF1, and HAS2. Important cancer genes affected by CNVs included TP53, BRCA1, BRCA2, ERBB2, IDH1, and IDH2. WES detected numerous mutations, some of which affecting BC associated genes as CDH1, HEPACAM, and LOXHD1. Using complementary molecular genetic techniques, this study identified shared and unshared molecular events in three highly aberrant BCBM emphasizing the challenge to detect new molecular biomarkers and targets with translational implications. Among new findings with the capacity to gain clinical relevance is the detection of overexpressed snoRNAs known to regulate some critical cellular functions as ribosome biogenesis.

Atypical prostatic hyperplasia (APH) is a pseudoneoplastic lesion that can mimic prostate adenocarcinoma because of its cytologic and architectural features. Suspension of date palm pollen (DPP) is an herbal mixture that is widely used in folk medicine for male infertility. The aim of the present study was to evaluate the effect of DPP suspension and extract on APH-induced rats.

Increased mesenchymal–epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumour progression. The aim of the present study is to explore the relationship between immunohistochemical expression of c-MET in colorectal carcinoma (CRC) and the clinicopathological characteristics and follow up data, to compare the expression of c-MET in primary CRC and its metastasis in lymph nodes and to test its validity as independent prognostic factor. Hundred and thirty-five archival CRC and nodal metastases samples were collected from King Abdulaziz University Hospital, Saudi Arabia. Tissue microarrays were constructed and immunohistochemistry was done to detected c-MET protein expression. Appropriate statistical analysis was performed. High c-MET immunostaining was significantly associated with tumour size larger than 5 cm (p < 0.003) and in left colon subsite (p < 0.05). There was no significant correlation between c-MET protein expression and age, sex, degree of differentiation, tumour invasion, presence of nodal metastasis, lymphovascular invasion, status of surgical resection margin, or presence of distant metastasis. Furthermore, no association between c-MET protein expression and disease free survival. High protein expression of c-MET is associated with the incidence of local disease recurrence (p < 0.012). c-MET is a new promising target that may help in understanding the pathogenesis of CRC, and to be used as independent prognostic biomarker to predict local disease recurrence in CRC. Further molecular in vitro and in vivo studies are required to pursue c-MET as potential molecular marker of metastases and test the possibility of its incorporation as a new targeted therapeutic target.

Red onion scales (ROS) contain large amounts of flavonoids that are responsible for the reported antioxidant activity, immune enhancement, and anticancer property. Atypical prostatic hyperplasia (APH) was induced in adult castrated Wistar rats by both s.c. injection of testosterone (0.5 mg/rat/day) and by smearing citral on shaved skin once every 3 days for 30 days. Saw palmetto (100 mg/kg) as a positive control and ROS suspension at doses of 75, 150, and 300 mg/kg/day were given orally every day for 30 days. All medications were started 7 days after castration and along with testosterone and citral. The HPLC profile of ROS methanolic extract displayed two major peaks identified as quercetin and quercetin-4′-β-O-D-glucoside. Histopathological examination of APH-induced prostatic rats revealed evidence of hyperplasia and inflammation with cellular proliferation and reduced apoptosis Immunohistochemistry showed increased tissue expressions of IL-6, IL-8, TNF-α, IGF-1, and clusterin, while TGF-β1 was decreased, which correlates with the presence of inflammation. Both saw palmetto and RO scale treatment have ameliorated these changes. These ameliorative effects were more evident in RO scale groups and were dose dependent. In conclusion, methanolic extract of ROS showed a protective effect against APH induced rats that may be attributed to potential anti-inflammatory and immunomodulatory effects.