p.1
KRAS Mutations and Colorectal Cancer
Which protein mutations lead to oncogenic activation in the Ras/Raf/Erk/Map kinase pathway?
Mutations in Ras protein, particularly at Gly 12, Gly 13, and Gln 61.
p.4
Pancreatic Cancer Genetic Alterations and Diagnostics
Which study identified over 1500 somatic mutations affecting 1007 genes in pancreatic cancers?
The study by Jones et al. (2008).
p.4
Pancreatic Cancer Genetic Alterations and Diagnostics
Which signaling pathways are commonly affected by gene mutations in pancreatic carcinogenesis?
EGFR/RAS/MAPK pathway, PI3K/AKT pathway, VEGF, WNT/β-catenin pathway, and TGF-β signaling.
p.4
Pancreatic Cancer Genetic Alterations and Diagnostics
What are pancreatic intraductal neoplasia (PanIN) and intraductal papillary-mucinous neoplasms (IPMNs) commonly associated with genetically?
They often contain KRAS, TP53, SMAD4, and p16/CDKN2A mutations.
p.4
Pancreatic Cancer Genetic Alterations and Diagnostics
What molecular marker panel could stratify patients into high-risk groups for pancreatic cancer?
A panel including methylated p16, p53 mutations, and KRAS mutations.
p.2
Molecular Testing for Colorectal Cancer Biomarkers
What is the predictive value of SMAD4 mutation/inactivation?
The predictive value of SMAD4 mutation/inactivation is controversial.
p.3
Familial Adenomatous Polyposis (FAP) and Genetic Testing
How is MYH polyposis inherited?
In an autosomal-recessive manner.
p.2
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
What is the response of patients with MSI-H colon cancers to 5-FU based treatment?
Patients with MSI-H colon cancers do not benefit from treatment with 5-FU.
p.2
Molecular Testing for Colorectal Cancer Biomarkers
What is the CpG island methylator phenotype (CIMP +), and what is it associated with?
CIMP + is characterized by simultaneous hypermethylation of the promoter regions of TSGs, found in approximately 20% of CRC patients, often linked with MSI, wild-type TP53, and BRAF mutation.
p.3
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
What defines MSI-H in tumor tissue compared to normal tissue control?
LOH in two or more of five markers.
p.4
Pancreatic Cancer Genetic Alterations and Diagnostics
What are the most common genetic alterations observed in pancreatic ductal adenocarcinomas (PDACs)?
PDACs frequently have loss of chromosomes 18, 17, 6, 21, 22, Y, 10, 4, 15p, 14p 5, 13p, 9p, 21p, and 17p. The most common event is allelic loss of chromosome 18 (about one-third of pancreatic carcinomas have a consensus region of homozygous deletion at 18q21).
p.1
BRAF Mutations and Their Impact on CRC Prognosis
What is the impact of BRAF mutations on CRC prognosis and response to treatment?
BRAF mutations are associated with worse survival and resistance to anti-EGFR monoclonal antibodies.
p.4
Pancreatic Cancer Genetic Alterations and Diagnostics
What genetic mutation is commonly seen in the Ashkenazi Jewish population and predisposes individuals to pancreatic cancer?
Germline mutations in BRCA2.
p.2
Molecular Testing for Colorectal Cancer Biomarkers
What is the significance of SMAD4 mutation in colorectal cancer (CRC) prognosis?
It is associated with poor prognosis following surgery and 5-fluorouracil (5-FU)-based adjuvant therapy.
p.2
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
What is the significance of MSI-H in colorectal cancer?
MSI-H tumors tend to be more proximally located, poorly differentiated, of mucinous histologic type, and linked with TGFBRII and BRAF mutations.
p.1
EGFR Monoclonal Antibodies in Cancer Treatment
What is one method used to detect increased EGFR copy number that has predictive value?
FISH (Fluorescence In Situ Hybridization).
p.4
Pancreatic Cancer Genetic Alterations and Diagnostics
What are some potential diagnostic markers for pancreatic cancers?
Detection of mutations of KRAS, telomerase (hTERT), and aberrant methylation of certain genes (e.g., p16/CDKN2A, APC, TSLC/IGSF4, SOCS-1, cyclin D2, RASSF1A).
p.2
Molecular Testing for Colorectal Cancer Biomarkers
What is HER2's role in colorectal cancer?
Approximately 3% of colorectal cancers show amplification of HER2, and both HER2-amplified and HER2-mutated cancers can show resistance to EGFR inhibitors.
p.3
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
What are the two rare but distinct variants of HNPCC?
Muir-Torre syndrome and Turcot syndrome.
p.4
Pancreatic Cancer Genetic Alterations and Diagnostics
What are the most frequent gene mutations in pancreatic cancers?
Activation of KRAS (95%), inactivation of p16/CDKN2A (75%-80% mutation and 15% hypermethylation), TP53 (80%), and inactivation of SMAD4 (95%).
p.1
Pancreatic Cancer Genetic Alterations and Diagnostics
What is the significance of p53 (TP53) mutations in colorectal cancer?
TP53 mutations indicate a major predictor of failure to respond to radiotherapy and chemotherapy, and they predict lower survival.
p.2
Molecular Testing for Colorectal Cancer Biomarkers
What is the association between chromosomal loss at 18q and CRC?
Chromosomal loss at 18q encompassing both SMAD2 and SMAD4 has been reported in up to 70% of CRCs.
p.2
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
Which MMR genes are primarily associated with HNPCC?
Mutations in MLH1 and MSH2 account for about 90% of identifiable mutations associated with HNPCC.
p.3
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
According to the Bethesda Guidelines, how many microsatellite markers must be tested for MSI?
Five microsatellite markers, including three dinucleotide repeats and two mononucleotide repeats.
p.1
EGFR Monoclonal Antibodies in Cancer Treatment
How common is EGFR mutation in colorectal cancer (CRC)?
It occurs in fewer than 1% of cases.
p.4
Pancreatic Cancer Genetic Alterations and Diagnostics
Which marker is associated with a worse outcome in pancreatic cancer?
Alterations of p16 and hTERT.
p.2
Familial Adenomatous Polyposis (FAP) and Genetic Testing
What are the characteristics of Familial Adenomatous Polyposis Syndrome (FAP)?
FAP is characterized by numerous colorectal polyps (usually more than 100) and is mainly attributable to the mutation/deletion of the APC gene.
p.3
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
Which genes are associated with Turcot syndrome?
Mutations in the MLH1 and PMS2 genes.
p.3
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
What is used for detecting MMR dysfunction in HNPCC?
Immunohistochemistry on paraffin-embedded tissues.
p.3
Familial Adenomatous Polyposis (FAP) and Genetic Testing
What are the notable extracolonic manifestations in MYH-associated polyposis?
Duodenal adenomas or carcinomas, and higher frequencies of ovarian, bladder, and skin cancers.
p.2
Molecular Testing for Colorectal Cancer Biomarkers
What is responsible for familial juvenile polyposis regarding SMAD4?
Inactivation of the SMAD4 gene through germline mutation and loss of the unaffected wild-type allele.
p.3
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
What cancers are associated with Muir-Torre syndrome?
Sebaceous skin tumors, small and large intestinal, gastric, kidney, endometrial, and ovarian cancer.
p.3
Familial Adenomatous Polyposis (FAP) and Genetic Testing
Which gene mutation causes Peutz-Jeghers Syndrome?
STK11 (also known as LKB1) gene.
p.3
Familial Adenomatous Polyposis (FAP) and Genetic Testing
What is MYH polyposis?
An inherited colon cancer syndrome due to mutations in the MYH gene.
p.1
KRAS Mutations and Colorectal Cancer
What percentage of CRC cases show KRAS mutation?
At least 35% to 45%, and up to 75% in some series.
p.3
Pancreatic Cancer Genetic Alterations and Diagnostics
What are the main types of genetic alterations in pancreatic cancer?
Mutations in KRAS, p53, p16, SMAD4, and MSI.
p.1
KRAS Mutations and Colorectal Cancer
What is the recommended action for patients with metastatic colon cancer who are candidates for anti-EGFR therapy?
They should be tested for KRAS mutations in a CLIA-accredited laboratory.
p.3
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
What cancers are associated with Turcot syndrome?
Glioblastoma and colorectal cancer (CRC).
p.1
PIK3CA Mutations and Resistance to Anti-EGFR Therapy
What are the commonly mutated exons in PIK3CA in CRC?
Exons 9 (E542K, E545K) and 20 (H1047R).
p.1
Familial Adenomatous Polyposis (FAP) and Genetic Testing
What role does the APC gene play in colorectal cancer?
APC mutations can initiate and promote carcinogenesis in sporadic CRCs.
p.2
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
What percentage of CRCs are associated with MSI (microsatellite instability)?
Approximately 15% to 20% of CRCs have MSI-H characterized by inactivation of mismatch repair (MMR) genes.
p.3
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
How is the diagnosis of HNPCC primarily determined?
Based mainly on clinical information and familial history.
p.3
Familial Adenomatous Polyposis (FAP) and Genetic Testing
What is Familial Juvenile Polyposis Syndrome (JPS)?
A rare disorder inherited in an autosomal-dominant fashion in at least 30% of patients.
p.2
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
What is the inheritance pattern of Hereditary Nonpolyposis Colorectal Cancer (HNPCC or Lynch Syndrome)?
HNPCC is an autosomal-dominant genetic condition.
p.3
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)
Which genes are associated with Muir-Torre syndrome?
Mutations in the MSH2 gene.
p.3
Familial Adenomatous Polyposis (FAP) and Genetic Testing
What characterizes Peutz-Jeghers Syndrome (PJS)?
Melanotic mucocutaneous hyperpigmentation and gastrointestinal hamartomas.
p.3
Familial Adenomatous Polyposis (FAP) and Genetic Testing
What defines Serrated Polyposis Syndrome?
Presence of approximately 100 hyperplastic or serrated polyps or sessile adenomas.
p.3
Familial Adenomatous Polyposis (FAP) and Genetic Testing
What is the risk increase for developing CRC in subjects with biallelic MYH mutations?
A 177-fold increase compared to the general population.
