Question

Clinical Cancer Case Study 1

Nancy is a 53-year-old female. Nancy spends every day at her local YMCA teaching a Zumba class and is very active in her community. For the last month, she has been bothered by persistent pelvic pain and intermittent vaginal bleeding even though she started menopause last February. She mentioned this to her daughter during a lunch date and because of her daughters urging, Nancy has made an appointment to see her primary care physician.

The doctor performs a pelvic exam and orders a CBC with CA 125 screening, a pelvic ultrasound and a biopsy.

Her CBC was normal but her CA 125 levels were 75 kU/L.

A pelvic mass was identified by pelvic ultrasound and the biopsy indicated the presence of adenocarcinoma cells within the endometrium.

Due to these results, a CT scan and a radical hysterectomy which will remove the uterus, tissue on the sides of the uterus, the cervix and the top region of the vagina, was scheduled for Nancy.

The surgeon sent the tumor to be genetically profiled. The following gene mutations were found in the tumor.

PTEN

TP53

ZFHX3

FGFR2

SOX17

ANK3

CTNNB1

PIK3R1

CCND1

You are the genetic counselor who just received the genetic profile of Nancy’s tumor. It is your job to completely understand how the cells in this tumor have changed and how this affects their function and potential to metastasize throughout the body.

Answer the following questions to complete the report which will help Nancy understand her specific tumor type and which treatments will work best for her.

1. What type of cancer do you conclude that Nancy has? What signs, symptoms and results led to this conclusion?

2. With the online genomic tools we have been using in class, determine the following about the tumor’s genomic profile. For each mutated gene describe in complete sentences:

A. Full name of gene

B. Cellular localization of genomic product (nuclear, cytoplasmic, mitochondrial etc.)

C. Detailed description of function of genomic product within a normal cell (ex. If part of a pathway, describe the pathway components and where this gene product fits in the pathway and its role in the pathway)

D. Detailed description of what type of mutations have been found for each gene within this tumor and possible ways this may affect or change cellular function. Use the resource Cosmic Genomes Catalogue of Somatic Mutations from a Human Cancer Genome

E. Role this gene plays in tumor phenotype and metastatic potential.

F. Frequency this gene is mutated in this type of cancer.

3. From the information you have compiled about the genomic profile of the tumor, write a summary for the patient about the likelihood of this tumor to become fully metastatic and spread to other parts of the body.

Question:

I'm having a hard time with the second part of this Assignment. I've tried using NCBI blast for it but i'm not sure if i'm supposed to do it that way? If so why am i getting a pop-up that "No significant similarity was found?" Also for Question 3,what exactly should i be comparing?

Answer 1

Answer 1: From the physiological observations and the gene that has been mutated, it is concluded that Nancy has invasive cervical cancer. The genes that has been mutated are involved in the cell cycle regulator and tumour suppression. Pelvic pain and postmenopausal vaginal bleeding are most important symptoms of the invasive cervical cancer. CA 125 or Cancer Antigen 125 is a protein that is found in higher amount in the blood of patients with ovarian cancer.

Answer 2:

i) PTEN – PTEN gene encodes a protein, Phosphatase and tensin homolog. The cellular localization of genomic product is nuclear. Mutation in this gene develops cancers. This gene acts as a tumour suppressor gene. The phosphatase protein is involved in regulation of the cell cycle preventing cells from growing and dividing too rapidly.

ii) TP53 – TP53 gene encodes tumour suppressor protein p53. The cellular localization of genomic product is nucleus, endoplasmic reticulum, cytoskeleton and mitochondria. It regulates cell division by keeping cells growth and division under control.

iii) ZFHX3 – ZFHX3 gene encodes Zinc finger homeobox protein 3. The cellular localization of genomic product is nucleus. This protein is a transcriptional regulator which act as an activator or a repressor. It is a regulator of myoblast differentiation. Its expression is higher in the tumour cells.

iv) FGFR2 - FGFR2 gene encodes fibroblast growth factor receptor 2. The cellular localization of genomic product is Golgi apparatus, plasma membrane and extracellular region. The protein is a tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors. It plays essential role in the regulation of cell differentiation, proliferation, migration, apoptosis and embryonic development.

v) SOX17 - SOX17 gene encodes transcription factor SOX-17. The cellular localization of genomic product is nucleus. It is a transcription regulator protein that binds target promoter DNA and bends the DNA. It regulates transcription via Wnt signalling. It has important role in embryonic and postnatal vascular development. It assists in generating and maintaining fetal hematopoietic stem cells. It acts as a transcriptional activator in the premeiotic germ cells.   

vi) ANK3 - ANK3 gene encodes protein Ankyrin-3. The cellular localization of genomic product is Golgi apparatus, lysosome, cytoskeleton and plasma membrane. It is a membrane-cytoskeleton linker. It participates in the maintenance of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments.

vii) CTNNB1 - CTNNB1 gene encodes protein Catenin beta-1. The cellular localization of genomic product is nucleus, cytoskeleton and plasma membrane. This protein is a component of the canonical Wnt signalling pathway. It is involved in the regulation of cell adhesion. It is a component of an E-cadherin:catenin adhesion complex. It acts as a negative regulator of centrosome cohesion. It promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle.

viii) PIK3R1 - PIK3R1 gene encodes protein phosphatidylinositol 3-kinase regulatory subunit alpha. The cellular localization of genomic product is nucleus, cytosol, endoplasmic reticulum, Golgi apparatus and plasma membrane. It binds and activates protein-Tyrosine kinases. It has important role in the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues.

ix) CCND1 - CCND1 gene encodes protein G1/S-specific cyclin-D1. The cellular localization of genomic product is nucleus. This protein regulates the cyclin D1-CDK4 complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G1/S transition.