Pathology 1 - Block 2 - Part 3

davidwurbel7's version from 2016-04-17 03:28

Neoplasia 3

Question Answer
1. Self-sufficiency in growth signals 2. Insensitivity to growth inhibitory signals 3. Altered cellular metabolism (not discussed) 4. Evasion of apoptosis 5. Limitless replicative potential 6. Sustained angiogenesis 7. Ability to invade & metastasize 8. Ability to evade host immune responseEssential Alterations for Malignant Transformation
Growth Factor: Platelet Derived Growth Factor (PDGF)
Growth Factor Receptor: Platelet Derived Growth Factor Receptor (PDGFR)
Question Answer
Astrocytoma, Glioblastoma multiforme, and osteogenic sarcoma are associated with this growth factorPDGF
Proto oncogene: protooncogene SIS
Low grade astrocytoma, Glioblastoma multiforme, and osteogenic sarcoma are examples of cancers that use PDGF, produce PDGF Receptors due to the protooncogene SIS
Question Answer
Mutations, gene rearrangements and overexpression are three ways in which these can be activatedGrowth Factor Receptors
Protooncogene seen in Multiple Endocrine Neoplasia (MEN, types 2A, 2B and familial medullary carcinoma of thyroid)RET
Protooncogene seen in in gastrointestinal stromal tumor (GIST)c-KIT
Protooncogene seen in myeloid leukemiasFLT3
Protooncogene seen in pancreatic adenocarcinomasRAS
Gene rearrangements of this gene in LymphomasALK
Overexpression of these receptors seen in subset of lung adenocarcinomaERB-1
Overexpression of these receptors is amplified in 25% of all breast cancersERB-2 (Her-2/Neu)
Point mutations of RAS family genes constitute the most common type of abnormality involving proto-oncogenes in human tumors of which mutations in this RAS family member is most commonKRAS
Cholangiocarcinomas in addition to RAS mutations made be causes by thisLiver Fluke
90% of pancreatic adenocarcinomas and cholangiocarcinomas and 50% of colon have higher frequency of mutations in this geneRAS
Mutations in this gene is seen in almost all cases of hairy cell leukemias in more than 60% of melanomasBRAF
Mutations in this gene is seen in breast carcinomas and endometrial carcinomasPI3K
Mutations involving ‘non receptor’ tyrosine kinase. Mutation takes form of chromosomal translocation or rearrangement. C-abl is translocated from chromosome 9 to bcr region of chromosome 22, resulting in a fusion gene. Resultant chimeric gene encodes a constitutively active, oncogenic BCR-ABL tyrosine kinaseChronic Myelogenous Leukemia (CML)
Translocations of the MYC gene on chromosome 8 that lead to increased MYC protein levels. Translocation partner for MYC is usually the IgH locus t(8; 14). Associated with EBV infection and malariaBurkitt Lymphoma
Burkitt Lymphoma is associated with this translocation8; 14
Burkitt lymphoma is associated with this geneC-MYC
Neuroblastoma is associated with this geneN-MYC
Tumor that originates most frequently in the adrenal glands, posterior mediastinum, neck, or pelvis but can arise in any sympathetic ganglion. N-MYC geneNeuroblastoma
Presence of this in Neuroblastoma is a poor prognostic indicatorN-MYC Amplification
A gain of function in this through mutation will lead to cancer (Mantle Cell Lymphoma, breast carcinoma, and esophageal carcinoma) Cyclin D1
Familial melanona is associated with a germline mutation of this geneCDKN2A
In the familial type of this condition, both normal alleles of the RB locus must be inactivated. Chromosome locus 13q14Retinoblastoma
Children that have retinoblastoma are likely to have this as a second malignancyOsteosarcoma
Glioblastoma, Small cell carcinoma of lung, Breast cancer are the result of somatic mutation of this geneRB Gene
A germline mutation of p53 will lead to this familiar conditionLi-Fraumeni Syndrome
Germline loss-of-function mutations involving the APC. Thousands of polyps develop in the colon during their teens or early twenties one or more of these polyps undergoes malignant transformation, giving rise to colon cancerFamilial Adenomatous Polyposis
The function of the APC protein is to hold this activity in checkβ-Catenin
A somatic mutation of APC can lead to this in 50% of patientsHepatoblastomas
Diagnosed by at least 100 polyps. Colorectal adenocarcinoma develops in 100% of untreated FAP patients, often before age 30 and nearly always by age 50Familial Adenomatous Polyposis (FAP)
This mutation of CDKN2A is associated with Familial melanomaGermline Mutation
This gene along with CDKN2A is associated with familial melanomaBAF
This mutation of CDKN2A is associated with bladder cancers, head and neck cancersSporadic Mutation
Mutational inactivation of SMAD4 is common in these cancersPancreatic Cancers
Patient complains of abdominal pain, change in stools, jaundice, puritis (due to deposition of bile salts in the skin) and excoria seenPancreatic Head Cancer
A mutation of this gene frequent benign growths, such as skin appendage tumors, and an increased incidence of epithelial cancers: breast, endometrium, and thyroidPTEN
Clinical features: neurofibromas (benign), café-au-lait, Lisch nodules (hamartomas in iris), association with phaeochromocytomaNeurofibromatosis 1 (NF-1)
Germline mutations of neurofibromin 2. Benign bilateral schwannomas of the acoustic nerve. Patients frequently becomes paralyzed and deafNeurofibromatosis 2 (NF-2)
Somatic mutations of neurofibromin 2 affecting both allele is associated withSporadic Meningiomas and Ependymoma
Mutations in chromosome 3p are associated with hereditary renal cell cancers, pheochromocytomas, hemangioblastomas of the central nervous system, retinal angiomas, and renal cystsvon Hippel-Lindau (VHL)
Composed of chromaffin cells, which synthesize and release catecholamines. 10% of sporadic adrenal pheochromocytomas are bilateral. 10% biologically malignant, defined by the presence of metastatic disease. 10% are not associated with hypertensionPheochromocytoma
Clinical Features - hypertension, seen in 90% of patients. Many patients with hypertension demonstrate paroxysmal episodes, which are described as an abrupt, precipitous elevation in blood pressure, associated with tachycardia, palpitations, headache, sweating, tremor, and a sense of apprehensionPheochromocytoma
Lab diagnosis - elevated urinary excretion of free catecholamines and their metabolites, such as vanillylmandelic acid and metanephrinesPheochromocytoma
located on chromosome 11p13. WT1 protein is a transcriptional activator of genes involved in renal and gonadal differentiation. Pediatric tumor that is always malignantWilms Tumor (WT)
85% of patients with this cancer has a t(14;18) translocation this leads to overexpression of Bcl-2 protein. Overexpression of Bcl-2 protein then upregulates anti-apoptotic propertiesB Cell Lymphoma (Follicular Lymphoma)
Enzyme activity seen in almost all tumor cells which then prevents shortening of telomereTelomerase
New vessels are formed from previously existing capillaries or endothelial cells are recruited from bone marrow (vasculogenesis)Neovascularization
Breach the basement membrane, then cross the interstitial connective tissue then, enter the circulation by penetrating the basement layer of vascular channelInvasion
Once a tumor cell mass enters the vein, the tumor cell mass covers itself with thesePlatelets
Tumor cells may use this as a homing marker for an area of metastasisCD 44
Detachment of tumor cells from each other is accomplished by down-regulation of theseE-Cadherins
The basement membrane is degraded either by secreting proteolytic enzymes themselves or by inducing stromal cells to produce thisMetalloproteinases (MMPs)
Place at which a tumor arises from the indigenous cellPrimary Cancer
Place at which a tumor displaces indigenous cells in another siteSecondary Cancer
A defect in a family of genes encoding a group of proteins that work together to carry out DNA mismatch repair mismatch-repair factors correct the defect that may occur if mutated, errors accumulate throughout the genomeHereditary Nonpolyposis Colon Cancer (HNPCC)
Hereditary Nonpolyposis Colon Cancer (HNPCC) is the result of a defect in this repair mechanismDNA Mismatch Repair
The most common gene mutations associated with HNPCCMSH1 and/or MLH1
Regions containing short repeating sequencesMicrosatellites
Inherited disorder involving defective DNA repair genes. Increased risk of skin cancersXeroderma Pigmentosum
Xeroderma Pigmentosum is due to a defect in this DNA repair mechanismNucleotide Excision Repair (NER)
Mutations of these are associated with breast carcinoma and ovarian cancers (male breast cancers too) first degree relatives, pre menopausal womenBRCA1 and BRCA2
Mutation related to breast carcinoma, ovarian carcinoma, in men prostatic carcinomaBRCA1
Mutation related to breast carcinoma (in women and men), ovarian carcinoma, prostatic carcinoma, pancreatic carcinoma, bile ductsBRCA2