ABGC Boards - Final Review Questions and Answers 100% Pass

ABGC Boards - Final Review Questions and Answers 100% Pass Hereditary Breast and Ovarian Cancer - ANSWER -BRCA 1/2 Breast 50-87% Second primary tumor 50-64% BRCA 1: 20-45% BRCA 2: 10-30% BRCA 2: Male breast 6-10% Li-Fraumeni Syndrome - ANSWER --Sarcoma, breast, leukemia, adrenal and many others -May present in almost every way (ie all family members with same cancers or all with different) -Adrenocortical carcinoma considered pathognomonic -50% have some type by 30, 90% by age 60 -TP53 accounts for 70% of individuals Beckwith-Wiedemann - ANSWER -Overgrowth disorder in children, tongue, viscera, hemihyperplasia, abdominal wall defects, ear pits and creases. Pancreatic hyperplasia leads to neonatal hypoglycemia and MR Airway and feeding difficulties, Methylation abnormalities/imprinting disorder 11p15.5 (need mom, dad is shut off) 2 | P a g e Created by Grace Amelia © 2025, All Rights Reserved. -Childhood embryonal tumors (7.5%), Wilms (Kidney), hepatoblastoma, neuroblastoma, rhabdomyosarcoma hepatoblastoma - ANSWER -malignant liver tumor, most common primary liver malignancy in children, associated with BWS Wilms tumor - ANSWER -AKA kidney tumor, associated with BWS oncogene - ANSWER -A gene having the potential to cause a normal cell to become cancerous. Lynch Syndrome - ANSWER -cancer predisposition syhndrome affecting increased 50-80% risk for colon cancer before age 50 caused by germline pathogenic variant in one of four mismatch repair genes (MMR) -MSH2 -MSH6 -MLH1 -PMS2 MLH1 and MSH2 variants account for approximately 90% of pathogenic variants -Germline deletions in EPCAM inactivate MSH2 3 | P a g e Created by Grace Amelia © 2025, All Rights Reserved. Adrenocortical carcinoma - ANSWER -Cancer of the outer layer of the adrenal glands, commonly associated with Li-Fraumeni Syndrome 1.) MSI/MMR histochemistry (MSH2/MSH6 complexes, where MSH6 is absent if MSH2 is), (MLH1/PMS2 complexes where PMS2 is absent if MLH1 is absent) -MSH2 causes loss of MSH6 -MLH1 causes loss of PMS2 2.) BRAF (sporadic) 3.) If BRAF neg, methylation neg, proceed to MMR genetic testing - ANSWER -What is the testing algorithm for lynch syndrome? Familial adenomatous polyposis - ANSWER -Onset with hundreds of polyps forming in colon and rectum (at least 10-20 cumulative) -Mostly inherited -Classic (polyps at age 16) Cancer by 50 vs Attenuated (start of disease later in life and fewer than 100 polyps develop) -Hepatboblastoma -Desmoid tumor -Genetic testing of APC gene Cowden Syndrome - ANSWER -Lifetime risk of ~35% to develop thyroid cancer, associations with benign thyroid disease (adenoma, multinodular goitar) 4 | P a g e Created by Grace Amelia © 2025, All Rights Reserved. Other cancers and family history clues: breast cancer, endometrial cancer, follicular thyroid cancer, GI hamartomas, macrocephaly, mucocutaneous lesions, macular pimentation, autism, colon cancer, lipomas, renal cell carcinoma, intellectual disability, vascular anomalies Gene involved: PTEN hamartoma - ANSWER -mostly benign, focal malformation that resembles a neoplasm in the tissue of its origin. This is not a malignant tumor, it grows at the same rate as the surrounding tissue. It is composed of tissue elements normally found at that site, but they are growing in a disorganized manner. Multiple Endocrine Neoplasia Type 2 - ANSWER -Medullary thyroid cancer risk, pheochromocytomas, Hyperparathroidism (elevated blood calcium, hypercalcemia=osteoporosis, kidney stones, fatigue, generalized aches, depression, impaired concentration, constipation, hypertension) -MEN2A -MEN2B -FMTC RET testing offered to all patients with medullary thyroid cancer Pheochromocytoma - ANSWER -tumor of the adrenal medulla tissue characterized by increased formation of catecholamines Multiple Endocrine Neoplasia Type 2A - ANSWER -Diagnosed by 2 or more endocine tumors in a single person or in close relatives 5 | P a g e Created by Grace Amelia © 2025, All Rights Reserved. -95% lifetime risk for medullary thyroid cancer, average diagnosis in late teens with 1/2 having lymph node metastases at diagnosis -Half the time includes pheochromocytomas -Parathryoid adenoma or hyperplasia Multiple Endocrine Neoplasia Type 2B - ANSWER --Early and very aggressive medullary thyroid cancer (100% lifetime risk) -causes multiple tumors on the mouth, eyes, and endocrine glands -Most often de novo Peutz-Jeghers Syndrome - ANSWER --Mostly benign Hamartomatous polyposis, develop hamartomas in the small intestine (and other places) (colorectal, gastric, pancreatic, breast, and ovarian cancers) -Hyperpigmented macules on the mouth and hands -1/3 of children have symptomatic GI polyps before age 10 -Caused by STK11 (considered a breast cancer gene) Multiple Endocrine Neoplasia Type 1 - ANSWER -1.) Hyperparathyroidism 2.) Pancreatic/Gastric tumors 3.) Benign pituitary tumors (controls GH, TSH, Prolactin) MAP (MYH associated polyposis) - ANSWER -Greatly increased risk of colorectal cancer (43%-100%), associated with ten to a few hundred colonic adematous polyps that are evident at mean age of about 50 years 6 | P a g e Created by Grace Amelia © 2025, All Rights Reserved. -Between 1-10 polyps under age 40 -More than 10 between age 40-60 -More than 20 over 60 Autosomal recessive inheritance with common biallelic inheritance (test parents) in MYH gene low MSI instability CHECK2 - ANSWER -DNA repair gene that helps regulate BRCA1, modified Br Ca risk 1.5-3x gen population Others: colon, prostate, male breast, NBN - ANSWER -Forms complex with RAD50 which then interacts with ATM, increased cancer risks including brearst cancer BARD1 - ANSWER -gene mutation found in families that look like HBOC but dont have BRCA1/2 mutations, women with mutation have increased risk for breast cancer BRIP1 - ANSWER -gene with increased ovarian cancer risk, uncertain risk increase for breast ca AR disease: Fanconi Anemia Hereditary Diffuse Gastric Cancer Syndrome - ANSWER -High risk for diffuse type gastric cancer and lobular type breast cancer (56% to age 80 for men, 70% for men, family history pattern is positive 7 | P a g e Created by Grace Amelia © 2025, All Rights Reserved. Gene involved: CDH1 (e-cadherin protein) PALB2 - ANSWER -Partner and localizer of BRCA2, risk for breast cancer higher AR disease: Fanconi Anemia Fanconi anemia - ANSWER -physical abnormalities (ss, skin pigmentation, skeletal malformation ) , bone marrow failure, increased risk of malignancy (AML, solid tumors of head and neck) -Biallelic pathogenic variants in 18 genes (AR) -heterozygous pathogenic variant in RAD51 (AD) -hemizygous pathogenic variant in FANCB (XLD) B-ALL - ANSWER -recurrent cytogenetic abnormalities associated with this type of ca Acute-Promyletoic leukemia - ANSWER -PML/RARA fusion involved with this type of cytogenetic cancer CML - ANSWER -What cancer is the philadelphia chromosome responsible for creating t(9;22) present in 95% that has BCR/ABL fusion Oncogene - ANSWER -Arise from proto-oncogenes, which regulate cell signalling; Constitutive activation of these proto-oncogenes leads to tumors; 8 | P a g e Created by Grace Amelia © 2025, All Rights Reserved. Most often point mutations, but may be gene amplification, chromosome rearrangement (ex. BCR-ABL), viral insertion (ex. HPV); Ex. RET (MEN2) Tumor suppressor gene - ANSWER -Responsible for halting growth of damaged cells; Inactivation of these genes may lead to tumors (two-hit hypothesis); Ex. most hereditary cancer genes (BRCA1/2, NF1, APC) Mismatch repair gene - ANSWER -Identifies and repairs DNA errors made during replication; Gatekeepers and caretakers; Ex. Xeroderma pigmentosum, ATM, Lynch genes Incidence - ANSWER -Number of new cases of a disease per year Prevalance - ANSWER -Total number of cases in the population Mortality rate - ANSWER -Number of deaths per year per 100,000 people Survival rate - ANSWER -Proportion of people alive at some point subsequent to their diagnosis Relative survival rate - ANSWER -Survival rate adjusted for exp