A Case Study on PPM1D and 9 Other Shared Germline Alterations in a Family.

Background: The use of high-throughput genotyping techniques has enabled us to identify the rare germline genetic variants with different pathogenicity and penetrance, and understand their role in cancer predisposition. We report here a familial cancer case, a study from Western Indian.

Methods: NGS-WES was carried out in a lung cancer patient who has a family history of multiple cancers across generations, including tongue, lung, brain, cervical, urothelial, and esophageal cancer.

The Mystery of Cancer Resistance: A Revelation Within Nature.

Cancer, a disease due to uncontrolled cell proliferation is as ancient as multicellular organisms. A 255-million-years-old fossilized forerunner mammal gorgonopsian is probably the oldest evidence of cancer, to date. Cancer seems to have evolved by adapting to the microenvironment occupied by immune sentinel, modulating the cellular behavior from cytotoxic to regulatory, acquiring resistance to chemotherapy and surviving hypoxia.

Parental balanced chromosomal rearrangement leading to major genomic imbalance and an autosomal trisomy resulting in consecutive pregnancy loss: a case report.

Chromosomal aberrations such as parental balanced translocation contribute to a significant proportion of recurrent pregnancy losses. These have extreme genetic implications on the foetus which can either cause physical and/or mental retardation or early death. In this study, we report a unique clinical case of a couple with three consecutive pregnancy losses and we aim to determine the genetic abnormalities causing the miscarriages.

Apert syndrome with S252W FGFR2 mutation and characterization using Phenomizer: An Indian case report.

Human genetic disease needs differential diagnosis to optimize clinical management, enable prenatal detection, and genetic counselling. The current methods of robust DNA sequencing also require next generation phenotyping to match with for better interpretation of genotypic and phenotypic heterogeneity commonly observed. We report use of human ontology based phenotypic characterization with Phenomizer that gives statistical score for possible diagnoses based on which, the gene mutation was studied.

Titanium dioxide nanoparticles: an in vitro study of DNA binding, chromosome aberration assay, and comet assay.

Engineered titanium dioxide nanoparticles (TiO NPs) are extensively used in cosmetic, pharmaceutical and other industries globally due to their unique properties, which has raised concern for biosafety. Genotoxicity assessment is an important part of biosafety evaluation; we report in vitro cytogenetic assays for NPs considering their unique physicochemical characteristics to fill the gap of laboratory data regarding biological safety along with mechanistic study for mode of interaction of NP with genetic material. Comet and chromosome aberration assay (CA assay) using short-term human peripheral blood cultures following exposure to TiO NPs; along with physicochemical parameters for stability of nano form in cultures; and DNA binding activity were carried out.

Recurrent chromosomal translocations: Is proximity a rule?

The role of recurrent chromosomal translocations in pathogenesis is well characterized in many leukemia subtypes; however, the factors leading to such preferential gene fusions are yet to be understood. The proximity of the genetic regions is considered important for genetic exchange, and interphase molecular cytogenetic methods can be employed to measure the same. The interphase genomic location of gene pairs taking part in translocations which are non-randomly associated with leukemia subtypes was studied for the extent of proximity by measuring relative distance and radial location.

Familial Constitutional Rearrangement of Chromosomes 4 & 8: Phenotypically Normal Mother and Abnormal Progeny.

Balanced chromosome translocations carriers mostly do not have recognizable phenotypic expression but may have more risk of recurrent spontaneous abortions &/or children with serious birth defects due to unbalanced chromosome complements. Unbalanced chromosomal rearrangements have variable clinical expression and are rare. We present here a case report of three siblings affected with intellectual disability and minor dysmorphic features of face and limbs, born to a non-consanguineous couple in which mother had 5 abortions.

Constitutional Mosaic Trisomy 13 in Two Germ Cell Layers is Different from Patau Syndrome? A Case Report.

The heterogeneous phenotype of known syndromes is a clinical challenge, and harmonized description using globally accepted ontology is desirable. This report attempts phenotypic analysis in a patient of constitutional mosaic trisomy 13 in mesoderm and ectoderm to make globally comparable clinical description. Phenotypic features (minor/major abnormalities) were recorded and matched with the Human Phenotype Ontology terms that were used to query web-based tool Phenomizer.

Engineered nanoparticles: Revisiting safety concerns in light of ethno medicine.

The nanoparticles are a miracle invention of the century that has opened novel avenues of applications in various fields. The safety aspect of exposure to nanoparticles for humans, plants, animals, soil micro-flora, and ecosystem at large has been questioned. The safety concern can be addressed by laboratory studies to assess the actual risk and recommend exposure limits and related regulation.

Phenotypic spectrum in uniparental disomy: Low incidence or lack of study?

Context: Alterations in the human chromosomal complement are expressed phenotypically ranging from (i) normal, via (ii) frequent fetal loss in otherwise normal person, to (iii) sub-clinical to severe mental retardation and dysmorphism in live births. A subtle and microscopically undetectable chromosomal alteration is uniparental disomy (UPD), which is known to be associated with distinct birth defects as per the chromosome involved and parental origin. UPD can be evident due to imprinted genes and/or activation of recessive mutations.

Trisomy 8 in leukemia: A GCRI experience.

Trisomy of chromosome 8 is frequently reported in myeloid lineage disorders and also detected in lymphoid neoplasms as well as solid tumors suggesting its role in neoplastic progression in general. It is likely to be a disease-modulating secondary event with underlying cryptic aberrations as it has been frequently reported in addition to known abnormalities contributing to clinical heterogeneity and modifying prognosis. Here, we share our findings of trisomy 8 in leukemia patients referred for diagnostic and prognostic cytogenetic assessment.

Mutagen sensitivity in oral cancer patients, healthy tobacco chewers and controls.

Objective: To analyze chromosomal aberrations (CA) as an index of DNA damage, to measure DNA repair capability using mutagen sensitivity assay and to correlate tobacco exposure with CA.

Study Design: Oral cancer patients, healthy tobacco chewers and healthy tobacco nonusers were studied for spontaneous and mutagen-induced CA. An arbitrary unit obtained for lifetime tobacco exposure (LTE) was compared with CA.

Customized laboratory information management system for a clinical and research leukemia cytogenetics laboratory.

We developed a Microsoft Access-based laboratory management system to facilitate database management of leukemia patients referred for cytogenetic tests in regards to karyotyping and fluorescence in situ hybridization (FISH). The database is custom-made for entry of patient data, clinical details, sample details, cytogenetics test results, and data mining for various ongoing research areas. A number of clinical research laboratoryrelated tasks are carried out faster using specific "queries.

A Case of ABL-BCR Negative, Philadelphia Positive CML with t(5;9)(q13;q34).

The Philadelphia chromosome is found in more than 90 percent of chronic myeloid leukemia (CML) patients. In most cases, it results from the reciprocal t(9;22)(q34;q11), with the ABL proto-oncogene from 9q34 fused to the breakpoint cluster region (BCR) locus on 22q11. In 5 to 10 percent of patients with CML, the Ph originates from variant translocations, involving various breakpoints in addition to 9q34 and 22q11.

Atypical D-FISH patterns of BCR/ABL gene rearrangements in 169 chronic myeloid leukemia patients.

The Philadelphia (Ph) chromosome, a hallmark chromosomal anomaly observed in 95 percent of chronic myeloid leukemia (CML) cases, is known to involve the Abelson (ABL) proto-oncogene on chromosome 9 and the breakpoint cluster region (BCR) gene on chromosome 22, producing BCR/ABL mRNA encoding an abnormal tyrosine kinase protein. In the process of generating BCR-ABL fusion, the deletion of residual BCR or ABL occurs in 15-30 percent of CML patients. In addition, some rearrangements are complex, and do not yield the ABL/BCR fusion due to the involvement of a third chromosome in the rearrangement.