After the birth of the “cytogenetics” in 1956 and its application in medicine in 1959 as valuable tool for the diagnosis of congenital diseases caused by chromosomal abnormalities, its limitations persuades the investigators to discover and employ “banding” techniques. This method could overcome many pre-existing problems and limitations but was not diagnostic especially when tissue culture was not possible due to tissue necrosis or in microdeletions. Fortunately, Fluorescent In Situ HYBRIDIZATION (FISH) could prevail over many of the aforementioned limitations but it could not evaluate necrosed tissues since it required a specific probe for each disease. Array COMPARATIVE GENOMIC HYBRIDIZATION (aCGH) is a new technique which enables us to study both necrosed and viable tissues. Another advantage of this method is the ability to study the whole genome and assess any decrease or increase in the chromosome material. This technique is currently regarded as the best and most efficient. Since stillbirths and viable or necrosed curettage specimens comprise most of the referred specimens to Kariminejad & Najmabadi Pathology and Genetic Center and evaluation of the specimens with a special focus on chromosomal aberrations are required by clinicians, we have equipped our center with technical equipment and experienced cytogenetic technicians. In the end, two cases whose definite diagnoses were made using FISH and Array CGH are presented.

Chromosome microarray is being suggested and replacing karyotype as first tier diagnostic test for individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Chromosome microarray gives a diagnostic yield of 15-20% for genetic testing of individuals with DD/ID, ASD or MCA compared to 3% in karyotype (excluding Down syndrome and other recognizable chromosomal syndromes). We present the results of chromosome microarray performed on 110 individuals with DD/ID, ASD or MCA. From the 110 cases, 23 cases (20.9%) showed copy number variations, of which 13 were deletions, 5 were duplication and 5 were duplication and deletion. The limitations of chromosome microarray are for detection of balanced translocation and low-level mosaicism, but these chromosomal abnormalities are rare causes of abnormal phenotypes in this category of patients.

Objective: Array COMPARATIVE GENOMIC HYBRIDIZATION (Array-CGH) has been used in diagnostic laboratories for the evaluation of individuals with intellectual disability/developmental delay, autism spectrum disorders, multiple congenital anomalies/dysmorphic features, prenatal diagnosis, and products of conception. Clinically available whole-genome aCGH can detect unbalanced chromosomal rearrangements/abnormalities with coverage of about one probe per 6 kb to one probe per 70 kb. Materials and Methods: We report the aCGH results of 142 patients referred to Sarem Cytogenetic laboratory, Sarem Women's Hospital for cytogenetic analysis between 2017 and 2020. They comprised 60 prenatal cases using amniotic fluid, 52 cases of products of conception, and 30 peripheral blood samples for postnatal cases. Chromosome analysis and aCGH were done for most of the referred samples. Results: Four out of fifty-two aborted fetuses had pathogenic aCGH results including,two male fetuses with gain of whole chromosome 21 (compatible with trisomy 21), one male fetus with a gain of whole chromosome 9 (compatible with trisomy 9), and one female fetus with a pathogenic gain of 78. 2 Mb on 13q13. 3q34 and loss of 612 Kb on 20p13p13 which overlap with 175 and 7 OMIM genes, respectively. The later aborted fetus's karyotype result is 46, XX, der(20)t(13, 20)(q13, p13) which is originated from the father. Also, five out of sixty prenatal amnion fluid's analysis demonstrated pathogenic chromosomal abnormalities. Ten out of thirty postnatal peripheral blood samples showed abnormal chromosomal aCGH results. Conclusion: The results of this report emphasize the importance of the combination of classic karyotyping with aCGH in better management of the patients.

Background: Nonlethal genetic damage is the basis for carcinogenesis. As various gene aberrations accumulate, malignant tumors are formed, regardless of whether the genetic damage is subtle or large enough to be distinguished in a karyotype. The study of chromosomal changes in tumor cells is important in the identification of oncogenes and tumor suppressor genes by molecular cloning of genes in the vicinity of chromosomal aberrations. Furthermore, some specific aberrations can be of great diagnostic and prognostic value. COMPARATIVE GENOMIC HYBRIDIZATION (CGH) is used to screen the entire genome for the detection and/or location chromosomal copy number changes.Methods: In this study, frozen sections of 20 primary breast tumors diagnosed as invasive ductal carcinoma from the Cancer Institute of Imam Khomeini Hospital, Tehran, Iran, were studied by CGH to detect chromosomal aberrations. We compared histopathological and immunohistochemical findings.Results: HYBRIDIZATION in four of the cases was not optimal for CGH analysis and they were excluded from the study. DNA copy number changes were detected in 12 (75%) of the remaining 16 cases. Twenty-one instances of chromosomal aberrations were detected in total, including: +1q, +17q, +8q, +20q, -13q, -11q, -22q, -1p, -16q, -8p. The most frequent were +1q, +17q, +8q, -13q, similar to other studies. In three cases, we detected -13q, which is associated with axillary lymph node metastasis and was reported in one previous study. The mean numbers of chromosomal aberrations per tumor in metastatic and nonmetastatic tumors was 1.5 and 1, respectively. No other association between detected chromosomal aberrations and histopathological and immunohistochemical findings were seen.Conclusion: Since intermediately to widely invasive carcinomas are more likely to have chromosomal aberrations, CGH can be a valuable prognostic tool. Furthermore, CGH can be used to detect targeting molecules within novel amplifications which holds the potential for a new therapeutic approach for intractable cancer.