Glioblastoma is the world’s most prevalent, infiltrative, and aggressive form of malignant tumors affecting the human brain. Studies show that glioblastoma has a higher frequency of genomic mutations than any other type of human brain cancers and tumors. The glioblastoma human brain cancer due to genomic instability has developed more top therapy-resistant characteristics, which makes it hard to treat. Clinical genomic studies focused on cells related to the proliferation of glioblastoma, which is the Glioblastoma Stem Cells (GSCs) have helped identify the genetic pathways associated with the development of malignant brain tumors. Studies on the alterations in genetic structure in genetic pathways promote the understanding of the glioblastoma and the diagnostics of the malignancy of brain tumors among populations. This also helps in the detection of genomic alterations due to the development of glioblastoma and its genomic instability and the development of clinical therapies to counter the disease. Though number mutations are occurring in driver genes associated with the growth of glioblastoma, only genomic alterations in PTEN, TP53, EGFR, PIK3R1, PIK3CA, NF1, RB1, IDH1 and LoH have been focused on this review. The genomic mutations in the linked genetic pathways are responsible for the distinction of the development of glioblastoma as either primary or secondary glioblastoma. This review paper focuses on the genomic profiling of glioblastoma to outline the gene mutations that drive the prevalence and aggressiveness of malignant brain cancer. It explores the role of genetics in the pathophysiology of glioblastoma, liked genetic pathways, and the genomic alterations to these genetic pathways. The genomic mutation profiling of the malignant glioblastoma will help create an understanding of the relationship between the genetic pathways and the prevalence of the brain tumors. The genetic mutation analysis will of the glioblastoma further focus on the available therapies used in the management and treatment of glioblastoma and other potential therapies that are being developed or in clinical trial phases. The review will further focus on the future of glioblastoma diagnostics, prognosis, and the management of patients with the cancer.

Keywords: Genomic mutation, glioblastoma, altered genes, therapies, management.

BACKGROUND: The early stage of hypothyroidism is subclinical hypothyroidism which could developed to apparent hypothyroidism and cause adverse metabolic flaws, prevalence of hypothyroidism is high in chronic kidney disease (CKD) incidence, in inclusion to those undergoing dialysis. Various studies reveled association between functioning of thyroid and metabolic syndrome. However, association between FT3/FT4 ratio and the SCH are not elaborated. Though, this study is focused to assess the ratio FT3/FT4 in identifying ScHt in CKD patients. METHODS: In a prospective case control study 53 known CKD samples underwent hemodialysis and 60 normal sample were opted for the study. Both control and CKD samples contain serum creatinine a is measured and evaluation of glomerular filtration rate (GFR) is calculated to know function of kidney and thyroid parameter serum FT3, FT4and TSH were measured for determining the FT3/FT4 ratio. RESULTS: Thyroid stimulating hormone levels were remarkable enhanced in patients without undergoing dialysis and with CKD in comparison to control groups (P<0.034). FreeT3 level was significantly less (P<0.001) and FT4/FT3 ratio was significant higher (p< 0.001) in patients of CKD without undergoing dialysis in comparison of controls. The area under the curve (AUC) of ROC curve for the steady variables of serum FT4/FT3 ratio was 0.914 with CI: 0.832 to 0.997. CONCLUSIONS: Solely FT3, FT4 had very minute sensitivity in detection of subclinical hypothyroidism in chronic kidney disease. In this study we demonstrated that the FT4/FT3 ratio establishment was advantageous step in detection of sub clinical hypothyroidism in patients with chronic kidney disease.

KEY WORDS: Sub clinical hypothyroidism, FT4/FT3 ratio, chronic kidney disease.