Fluorescent In-Situ Hybridization is the Hand Mirror of Cytogenetics: A Rare Case of Near Tetraploidy in Pediatric Acute Lymphoblastic Leukemia

Identification of specific chromosomal changes has important prognostic and biological implications in childhood Acute Lymphoblastic Leukemia (ALL). ALL cases with 90 chromosomes are rare. Here, we report a case of near-tetraploidy in a 4 year old boy diagnosed with B-cell ALL, where the ploidy was identified by Fluorescent In- Situ Hybridization (FISH) and confirmed by Conventional Cytogenetics. Our aim was to enumerate multiple signals observed by FISH, and to confirm the same by cytogenetics. FISH on cytogenetically fixed air-dried slides was performed by using BCR/ABL and MLL probe .Two hundred cells were scored. BMA was cultured and G-banded metaphases were analyzed in accordance with ISCN 2013. The results of the FISH test showed more than two signals and cytogenetics revealed clones of near-tetraploidy with mn 90, karyotype: 90-92, 4nXXY,-Y,-10,-10,-13, +14, +17, along with normal clones. The tetraploidy condition compared to hyperdiploid ALL has a poorer prognosis and the rarity of these cases makes accounting on treatment decisions a supposition. Presently, the patient is on standard treatment for ALL (UK ALL regime A). The numerical abnormality detected by FISH was confirmed by cytogenetics, which facilitated in reporting the results of this case earlier than the defined turnaround time. Therefore author opines that FISH reports should also contain observed additional information along with positive or negative status of the requested test

Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India

Breast and/or ovarian cancer (BOC) are among the most frequently diagnosed forms of hereditary cancers and leading cause of death in India. This emphasizes on the need for a cost-effective method for early detection of these cancers. We sequenced 141 unrelated patients and families with BOC using the TruSight Cancer panel, which includes 13 genes strongly associated with risk of inherited BOC. Multi-gene sequencing was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. We were able to detect pathogenic mutations in 51 (36.2%) cases, out of which 19 were novel mutations. When we considered familial breast cancer cases only, the detection rate increased to 52%. When cases were stratified based on age of diagnosis into three categories,. 40 years, 40-50 years and >50 years, the detection rates were higher in the first two categories (44.4% and 53.4%, respectively) as compared with the third category, in which it was 26.9%. Our study suggests that next-generation sequencing-based multi-gene panels increase the sensitivity of mutation detection and help in identifying patients with a high risk of developing cancer as compared with sequential tests of individual genes

Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations

Breast and/or ovarian cancers are among the most common cancers in women across the world. In the Indian population, the healthcare burden of breast and/or ovarian cancers has been steadily rising, thus stressing the need for early detection, surveillance, and disease management measures. However, the burden attributable to inherited mutations is not well characterized. We sequenced 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers, using the TruSight Cancer panel which includes 14 genes, strongly associated with risk of hereditary breast and/or ovarian cancers. Genetic variations were identified using the StrandNGS software and interpreted using the StrandOmics platform. We were able to detect mutations in 304 (30.1%) cases, of which, 56 mutations were novel. A majority (84.9%) of the mutations were detected in the BRCA1/2 genes as compared to non-BRCA genes (15.1%). When the cases were stratified on the basis of age at diagnosis and family history of cancer, the high rate of 75% of detection of hereditary variants was observed in patients whose age at diagnosis was below 40 years and had first-degree family member(s) affected by breast and/or ovarian cancers. Our findings indicate that in the Indian population, there is a high prevalence of mutations in the high-risk breast cancer genes: BRCA1, BRCA2, TP53, and PALB2. In India, socioeconomic inequality limiting access to treatment is a major factor towards increased cancer burden; therefore, incorporation of a cost-effective and comprehensive multi-gene test will be helpful in ensuring widespread implementation of genetic screening in the clinical practice for hereditary breast and/or ovarian cancers