p.2
Gastrointestinal Stromal Tumors (GIST) and Genetic Mutations
What mutations are commonly found in gastrointestinal stromal tumors (GIST)?
KIT and PDGFRA mutations.
p.4
Gastrointestinal Stromal Tumors (GIST) and Genetic Mutations
How is the behavior of SDH-deficient GISTs different from conventional GISTs?
Behavior cannot be predicted based on size and mitotic activity, often multifocal and tend to metastasize to lymph nodes.
p.2
Diagnostic Techniques in Sarcoma and Tumor Genetics
What diagnostic method is used when Ewing sarcoma/PNET has a normal karyotype?
Fluorescence in situ hybridization (FISH).
p.4
Molecular Genetic Pathology of Sarcomas
What kind of sarcoma is leiomyosarcoma?
A malignant tumor of smooth muscle.
p.3
Fusion Genes in Sarcomas
What chromosomal translocation is found in dermatofibrosarcoma protuberans (DFSP)?
Dermatofibrosarcoma protuberans (DFSP) is characterized by a reciprocal chromosomal translocation t(17;22)(q11;q13.1) or a supernumerary ring chromosome derived from t(17;22), resulting in the fusion of the COL1A1 gene on chromosome 17 with the PDGFB gene on chromosome 22.
p.1
Molecular Classification of Ovarian Cancer
What genetic mutations are commonly found in Type I ovarian tumors?
Type I tumors often harbor somatic mutations in KRAS, BRAF, PIK3CA, ERB-2 (Her2/neu), CTNNB1, and PTEN.
p.4
Gastrointestinal Stromal Tumors (GIST) and Genetic Mutations
What drug is used to treat patients with metastatic GIST showing mutations in cKIT/PDGFRA?
Imatinib mesylate (Glivec/Gleevec).
p.1
High-Grade Serous Carcinoma (HGSC) Characteristics
What genetic pathways are usually not defective in HGSCs but common in Low-Grade Serous Carcinomas (LGSCs)?
HGSCs generally lack defects in the Wnt/β-catenin or PI3K/PTEN signaling pathways, which are common in LGSCs.
p.2
Fusion Genes in Sarcomas
What is a common translocation found in synovial sarcoma?
The SS18-SSX translocation.
p.3
Fusion Genes in Sarcomas
What is the typical translocation found in synovial sarcomas (SSs)?
Synovial sarcomas are characterized by t(X;18)(p11.2;q11.2), resulting in a fusion between the SS18(SYT) gene on chromosome 18 and one of the SSX genes on the X chromosome, creating SS18-SSX1, SS18-SSX2, or SS18-SSX4 chimeric genes.
p.3
Fusion Genes in Sarcomas
What translocation is recurrently found in epithelioid hemangioendothelioma, and what recent discovery was made regarding a subset of these tumors?
The recurrent translocation t(1;3)(p36.3;q25) in epithelioid hemangioendothelioma results in a WWTR1-CAMTA1 gene fusion. Recently, a subset of epithelioid hemangioma with atypical morphology was found to contain a YAP-TFE3 fusion partner.
p.1
BRCA1 and BRCA2 Genetic Alterations in Ovarian Cancer
What results from the genetic alterations in BRCA1 and BRCA2 in HGSCs?
These genetic alterations result in a loss of ability to repair DNA double-strand breaks, leading to chromosomal instability.
p.2
Fusion Genes in Sarcomas
Which fusion gene is commonly found in clear cell sarcoma?
EWSR1-ATF1 fusion product.
p.4
Gastrointestinal Stromal Tumors (GIST) and Genetic Mutations
In which syndrome can SDH-deficient GISTs occur?
Carney triad or Carney-Stratakis syndrome.
p.4
Fusion Genes in Sarcomas
What is a primary karyotypic abnormality found in aneurysmal bone cysts?
t(16;17)(q22;p13) translocation producing a CDH11-USP6 fusion product.
p.4
Multiple Endocrine Neoplasia (MEN) Syndromes
What are the primary features of Multiple Endocrine Neoplasia (MEN) syndromes?
A group of benign and malignant tumors in various endocrine organs like pituitary, thyroid, and parathyroid glands.
p.1
Molecular Classification of Ovarian Cancer
What types of tumors are included in Type I ovarian tumors?
Type I tumors include low-grade endometrioid carcinoma, mucinous carcinoma, and a subset of clear-cell carcinomas.
p.1
Genetic Mutations in Melanoma
What makes BRAF an attractive therapeutic target in melanoma?
The high mutation rate of BRAF in melanoma makes it an attractive therapeutic target.
p.4
Gastrointestinal Stromal Tumors (GIST) and Genetic Mutations
What mutation is responsible for resistance to imatinib mesylate in GIST?
D816V point mutations in cKIT exon 17.
p.4
Multiple Endocrine Neoplasia (MEN) Syndromes
What syndrome is characterized by tumors in the parathyroid glands, stomach, pancreas, and other organs?
Multiple endocrine neoplasia type 1 (MEN1 or Wermer syndrome).
p.1
Genetic Mutations in Melanoma
What signaling molecule is most important downstream of RAS in melanoma?
The most important signaling molecule downstream of RAS in melanoma is BRAF.
p.2
Fusion Genes in Sarcomas
Which fusion gene is commonly associated with myxoid/round cell liposarcoma?
t(12;16)(q13;p11) translocation involving DDIT3 and TLS.
p.3
Molecular Genetic Pathology of Sarcomas
What are the characteristics of fibroblastic tumors?
Fibroblastic tumors are rare, have a long clinical history prior to presentation, and late metastases. They predominantly occur in young adults aged from 2 to 70 years, and are frequently located in the trunk and extremities.
p.3
Fusion Genes in Sarcomas
What translocation is associated with hemangioma of bone?
A t(18;22)(q23;q12) translocation bridging the EWSR1-NFATC1 genes.
p.3
Gastrointestinal Stromal Tumors (GIST) and Genetic Mutations
What are the common mutations associated with gastrointestinal stromal tumors (GISTs)?
Gastrointestinal stromal tumors (GISTs) commonly have activating mutations in the cKIT gene in 75% to 80% of cases and in the PDGFRA gene in 5% to 10% of cases.
p.1
Genetic Mutations in Melanoma
What genetic alteration rarely coexist in melanoma?
NRAS and BRAF mutations rarely coexist in melanoma.
p.2
Fusion Genes in Sarcomas
What type of genetic rearrangement is commonly found in extraskeletal myxoid chondrosarcoma?
t(9;22)(q22;q12) involving NR4A3 and EWSR1.
p.4
Gastrointestinal Stromal Tumors (GIST) and Genetic Mutations
What has become a standard diagnostic tool for GIST?
Detection of overexpression or mutation of cKIT/PDGFRA.
p.4
Gastrointestinal Stromal Tumors (GIST) and Genetic Mutations
What gene mutations are found in many wild-type GISTs?
Mutations in succinate dehydrogenase (SDH) genes.
p.4
Fusion Genes in Sarcomas
What chromosomal rearrangement is commonly found in Nodular Fasciitis?
Rearrangement of USP6 (ubiquitin-specific peptidase 6) typically fused with MYH9.
p.3
Fusion Genes in Sarcomas
What genetic alteration is shared between giant cell fibroblastoma (GCF) and dermatofibrosarcoma protuberans (DFSP)?
Both giant cell fibroblastoma (GCF) and dermatofibrosarcoma protuberans (DFSP) share the t(17;22)(q11;q13.1) genetic alteration involving the COL1A1 gene.
p.1
Genetic Mutations in Melanoma
What pathway is activated by oncogenic RAS mutations in melanoma?
Oncogenic RAS mutations activate the RAS/RAF/MEK/ERK signaling pathway in melanoma.
p.2
Molecular Genetic Pathology of Sarcomas
What are the two main categories of sarcomas based on genetic alterations?
1. Sarcomas with specific genetic alterations. 2. Sarcomas displaying multiple complex karyotypic abnormalities.
p.2
Molecular Genetic Pathology of Sarcomas
What genetic amplification is commonly found in well-differentiated and dedifferentiated liposarcomas?
Amplification in the q14 to q15 regions containing the MDM2 gene.
p.3
Fusion Genes in Sarcomas
Which translocations characterize the majority of LGFMS cases?
The majority of LGFMS cases are characterized by a t(7;16)(q32–34;p11) translocation derived from the fusion of FUS and CREB3L2.
p.1
High-Grade Serous Carcinoma (HGSC) Characteristics
Are KRAS and BRAF mutations common in High-Grade Serous Carcinomas?
No, KRAS and BRAF mutations are rare in High-Grade Serous Carcinomas.
p.1
BRCA1 and BRCA2 Genetic Alterations in Ovarian Cancer
What is the lifetime risk for ovarian cancer in BRCA1 and BRCA2 mutation carriers?
The lifetime risk for developing ovarian cancer is 30%-60% for BRCA1 mutation carriers and 15%-30% for BRCA2 mutation carriers.
p.4
Gastrointestinal Stromal Tumors (GIST) and Genetic Mutations
What is the characteristic growth pattern of SDH-deficient GISTs?
Multinodular and plexiform growth pattern, almost always epithelioid in morphology.
p.3
Fusion Genes in Sarcomas
What is the most common histologic subtype of rhabdomyosarcoma (RMS) and what genetic translocation is frequently associated with alveolar RMS (ARMS)?
The most common histologic subtype of rhabdomyosarcoma (RMS) is embryonal RMS (ERMS), and the frequent genetic translocation associated with alveolar RMS (ARMS) is t(2;13)(q35:q14), which fuses the PAX3 gene with the FOXO1A gene.
p.1
High-Grade Serous Carcinoma (HGSC) Characteristics
What characterizes High-Grade Serous Carcinomas (HGSCs)?
HGSCs are characterized by high-grade nuclei, short latent precursor lesions, rapid tumor progression into invasive carcinoma, and high prevalence of TP53 gene mutations.
p.1
Molecular Classification of Ovarian Cancer
What types of tumors are included in Type II ovarian tumors?
Type II tumors include high-grade serous carcinoma, undifferentiated carcinoma, some clear-cell carcinomas, and malignant mixed Müllerian tumor.
p.2
Fusion Genes in Sarcomas
What genetic translocation is characteristic of Ewing sarcoma family tumors (ESFTs)?
t(11;22)(q24;q12) translocation involving FLI1 and EWSR1 genes.
p.4
Diagnostic Techniques in Sarcoma and Tumor Genetics
What diagnostic tests are useful for nodular fasciitis?
FISH- and PCR-based assays.
p.4
Molecular Genetic Pathology of Sarcomas
What pathway plays a crucial role in the development of leiomyosarcoma?
Activation of the PI3K-AKT pathway.
p.1
Genetic Mutations in Melanoma
How frequent are BRAF mutations in malignant melanomas?
BRAF somatic missense mutations are found in 66% of malignant melanomas.
p.1
BRCA1 and BRCA2 Genetic Alterations in Ovarian Cancer
Which genetic alterations are commonly found in HGSCs?
Most HGSCs have genetic and somatic alterations in BRCA1 and BRCA2 genes.
p.3
Fusion Genes in Sarcomas
What other notable translocations have been found in LGFMS?
A minority of LGFMS cases exhibit a t(11;16)(p11;p11) translocation resulting in the fusion of FUS and CREB3L1, and two cases have exhibited fusion of EWSR1 and CREB3L1.
p.3
Fusion Genes in Sarcomas
What genetic fusion is found in congenital fibrosarcoma (CFS)?
Congenital fibrosarcoma (CFS) contains a novel t(12;15)(p13;q25) translocation resulting in ETV6-NTRK3 gene fusion.
p.1
Molecular Classification of Ovarian Cancer
How does molecular classification categorize ovarian carcinomas?
Ovarian carcinomas are divided into Type I and Type II tumors based on their pattern of tumor progression and molecular genetic changes.
p.1
BRCA1 and BRCA2 Genetic Alterations in Ovarian Cancer
What proportion of ovarian cancers is attributed to defects in BRCA1 and BRCA2?
DNA repair defects involving BRCA1 and BRCA2 contribute to 10%-15% of ovarian cancers.
p.1
Molecular Classification of Ovarian Cancer
What is the mutation profile of Type II ovarian tumors?
Type II tumors are characterized by a high frequency of TP53 mutations and high levels of chromosomal instability.
p.1
BRCA1 and BRCA2 Genetic Alterations in Ovarian Cancer
Why are ovarian cancers with BRCA1 and BRCA2 mutations more sensitive to certain chemotherapeutic agents?
They are more sensitive because they are less able to repair DNA damage caused by agents like platinum drugs and PARP inhibitors.
p.1
Genetic Mutations in Melanoma
What is the common mutation found in BRAF in melanoma?
80% of BRAF mutations in melanoma involve a single base substitution of valine by glutamic acid at position 600 (V600E).
