Background: Breast cancer is the most common malignancy among women in both developed and developing countries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens the public health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimens poses a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumab in breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose a priority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumor angiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics (including simultaneous mutations of TP53 and HER-2 genes). Materials and Methods: Age, axillary lymph nodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined and correlations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathological characteristics were evaluated. Results: There were significant associations between simultaneous mutations of HER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2 subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than 50 years. Conclusions: Our results demonstrated that patients with simultaneous mutations of HER-2 and p53 genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligible for obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breast cancer for treatment with anti-angiogenic drugs in LMCs.

Human epidermal growth factor receptor (HER) status is an important prognostic factor in breast cancer. There is no globally accepted method for determining its status, and which method is most precise is still a matter of debate. We here analyzed HER2 mRNA expression by quantitative reverse transcription-PCR parallel, we performed a routine evaluation of HER2 protein by immunohistochemistry (IHC). To assess the (FISH) was used, substituting FISH when the results of IHC were ambiguous (2+) and for those IHC results that PCR is a prerequisite for determining the exact status of HER2.

Introduction Skeletal dysplasia is a common, clinically and genetically heterogeneous disorder in the human population. An increasing number of different genes are being identified causing this disorder. We used whole exome sequencing (WES) for detection of skeletal dysplasia causing mutation in a fetus affected to severe lethal skeletal dysplasia. Patient Fetus was assessed by ultrasonography in second trimester of pregnancy. He suffers from severe rhizomelic dysplasia and also pathologic shortening of ribs. WES was applied to finding of causal mutation. Furthermore, bioinformatics analysis was performed to predict mutation impact. Results Whole exome sequencing (WES) identified a homozygous frameshift mutation in the TMEM263 gene in a fetus with severe lethal skeletal dysplasia. Mutations of this gene have been previously identified in dwarf chickens, but this is the first report of involvement of this gene in human skeletal dysplasia. This gene plays a key role in the growth hormone signaling pathway. Conclusion TMEM263 can be considered as a new gene responsible for skeletal dysplasia. Given the complications observed in the affected fetus, the mutation of this gene appears to produce much more intense complications than that found in chickens and is likely to play a more important role in bone development in human.

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Background: Small supernumerary marker chromosomes (sSMCs) are chromosomal fragments with abnormal structures found in patients with fertility problems and developmental delay. They may be detected in amniotic cell karyotypes. sSMCs are categorized as hereditary or de novo. Here, we describe a case of prenatal de novo 4q11q12 sSMC and its molecular cytogenetic features which had no apparent phenotypic abnormality. Case: The fetus of a 36-yr-old pregnant woman was detected positive for Down’s syndrome (trisomy 21) at the 16th wk of gestation. Quantitative fluorescent polymerase chain reaction technique was applied for the rapid detection of numerical aneuploidy of chromosomes X, Y, 13, 18, and 21 microsatellites. Array comparative genomic hybridization (array CGH) technique was also conducted following the karyotype analysis of amniotic cells. The karyotype analysis was also done for the parents. Quantitative fluorescent polymerase chain reaction result revealed a male fetus with a normal chromosomal pattern, while the amniocentesis karyotype analysis identified a male fetus with a marker chromosome (47, XY, +mar), and the sSMC were existing in 100% of amniocyte metaphase spreads. The parents’ normal karyotypes indicated that the sSMC was de novo. Array CGH analysis revealed a 6.48-Mb duplication at 4q11q12. Eventually, the parents decided to terminate the pregnancy by legal abortion. Conclusion: Our study highlights the importance of the application of array CGH in combination with karyotype analysis for rapid and precise prenatal diagnosis of partial aneuploidy region.  Key words: Prenatal diagnosis, Array CGH, Chromosome 4, Chromosome markers.

In this study, we reported for the first time Y chromosome haplotypes throughout Iran from 1097 unrelated Iranian males using the AmpFlSTRTM YfilerTM kit. 1094 out of the 1097 haplotypes identified were unique. The values of haplotype diversity (HD) and discriminating capacity (DC) were 1.00000 and 0.997, respectively. An analysis of genetic distance was performed by the molecular variance (AMOVA) and multidimensional scaling plots (MDS), showing that a statistically was observed significant difference between the study population and previous data reported for other Iranian populations and other neighboring countries. The findings of the present study are likely to be useful for Forensic casework analysis and kinship investigations.

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