A 37-year-old woman presents with a four-month history of weight loss (20kg) and malaise. Medical history was otherwisenon-contributoryand she examined normally. She had a normal screening gastroscopy...

Running Head: Critical Analysis of Gene Mutations
Critical Analysis of Gene Mutations 9
Assessment
Critical Analysis of Gene Mutations
Case Study Presentation
The clinical symptoms of weight loss and malaise, in addition to non contributory and normal medical history, show abnormal clinical parameters. The detection of many lesions in lymph nodes, spleen, lungs and liver reflects undifferentiated primitive cells. These cells do not appear like healthy cells and seem very immature. Such primitive and undifferentiated cells fall under grade 4 of tumor cells (National Cancer Institute, 2020).
Rapid Next Generation Tumor Sequencing is an important method to sequence the complete genome or capture a large amount of genetic information regarding the cancer (Morash, Mitchell, Beltran, Elemento & Pathak, 2018). It has faster turnover time, is less costly and can detect multiple abnormalities in less amount of DNA (Morash et al., 2018).
The tumor sequencing revealed ‘Metastatic Malignancy of Unknown Primary’. In this condition, there are 40-45% chances that the lymph is most widely affected organ (Zaun, Schuler, Herrmann & Tannapfel, 2018). However, it is a rare illness, where malignant cells may develop in any part of the body but the primary origin of cancer is unknown. The cancer may spread to other parts of the body through metastasis. In initial presentation, there are no identified primary tumors.
The normal gastroscopy and colonoscopy reveals that the patient has no cancer in these organs. It requires regular screening and follow up care to manage the potential incidence of malignancy.
The two mutations identified in rapid tumor pipeline, were:
· BRAFc.1799T>A
· CDKN2Ac.212A>G
This assignment is aimed to critically evaluate the literature over these mutations. It will also describe the molecular and clinical aspects of the case and will discuss their significance in terms of diagnosis and management.
Evaluating the literature over identified mutations
About 90% of these BRAF mutations take place at the 600 residue (American Type Culture Collection [ATCC], 2020). It is present at the activation domain of kinase. The mutations in these genes are mostly mutually exclusive. Additionally the BRAF mutations are found in increased number in nevi which shows their role in early stage of neoplastic process. The mutations in CDKN2A allow the tolerance of BRAF mutation to be coexisting at the same location in cells.
The location of CDKN2A gene is 9p21 in human genome and it is mostly deleted or mutated in majority of the carcinogenic cells. The promoter area of this gene is hypermethylated in carcinogenic cells which leads to silencing and reduced expression of this gene. Immuno histochemistry of this gene sequence shows wide range of findings for melanocytic lesions. However in melanomas, the complete loss of p16 labeling or loss of expression is associated with melanomas rather than nevi. The histochemistry of p16 is used by the dermatopathologists in differentiating nevi from the melanoma cases.
Both these genes are found in two variants: Heterozygous and homozygous. Heterozygous shows that two different formats of same gene are found in a person. The heterozygous mutation shows the mutation in any one allele of that gene. Homozygous shows the person has two same type of genes for a particular trait. It is a mutation of both the alleles of gene.
Molecular and Clinical Aspects of the Case
Several patients having cancer of unknown primary origin, have more than one areas of the body involved in multiple visceral sites such as bone, lymph nodes, liver and lungs. The CT scan of chest, pelvis and abdomen showed multiple lesions over spleen, lungs, liver and lymph nodes. The condition is known as Sarcoidosis. The metastatic malignancy of unknown primary is defined by the presence of metastasis without any primary origin of tumors. A direct prognostically favorable search for the primary origin is essential to treat the condition at an early stage.
The Carcinoma of unknown primary (CUP) comprises of 2-5% of all the cases of cancers globally (Palmucci, Torrisi & Caltabiano, 2016). The primary tumor site may escape the clinical diagnostic tests or may disappear after initiating the metastasis. It may also be eliminated by the defense system of the body. The CUP has also been associated with chromosomal or genetic abnormalities known as mutations. Sometimes Aneuploidy and overexpression of certain genes like Bcl-2, Ras, p53 and Her-2 has been found to be involved in CUP. However these mutations do not cause any impact on effectiveness of therapy...