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Genetic Counseling Boards > Cancer Genetics > Flashcards

Cancer Genetics Flashcards

1
Q

Six Features of Cancer Cells

A
  • independence of external growth signals
  • insensitive to anti-growth signals
  • ability to avoid apoptosis
  • ability to replicate indefinitely
  • ability to trigger angiogenesis
    and vascularize
  • ability to invade tissues and establish secondary tumors
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2
Q

t(8;14)(q24;q22)

A

Burkitt’s lymphoma; MYC gene translocated next to immunoglobulin gene

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3
Q

t(9;22)

A

Philadelphia chromosome; BCR-ABL fusion oncogene causing chronic myeloid leukemia

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4
Q

Four Classes of Cancer Regulatory Genes

A
  • protooncogenes/oncogenes
  • tumor suppressor genes
  • apoptosis regulation genes
  • DNA repair genes
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5
Q

Oncogenes

A
  • “too much gas”
  • GoF mutation that is dominant at cellular level and promotes uncontrolled cell growth
  • Examples: Her2, BCR-ABL, RAS family
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6
Q

Tumor Suppressor Genes

A
  • “no brakes”
  • LoF mutation that is recessive at cellular level and leads to loss of cell division control
  • Examples: RB1, BRCA1/2, NF1/2, etc
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7
Q

Apoptosis Regulation Genes

A
  • “energizer bunny”
  • damaged cell does not undergo programmed cell death
  • Examples: TP53
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8
Q

DNA Repair Genes

A
  • “no quality control”
  • enzymes lose function to repair DNA appropriately
  • seen in both heterozygous and homozygous states
  • Examples: ATM/ataxia telangiectasia, NBN/Nijmegen breakage, Bloom, Fanconi anemia
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9
Q

Population Risk - Prostate Cancer

A

14%

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10
Q

Population Risk - Breast Cancer

A

12-13%; <1% in males

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11
Q

Population Risk - Colorectal Cancer

A

4-5%

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12
Q

Population Risk - Pancreatic Cancer

A

1.5%

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13
Q

Population Risk - Ovarian Cancer

A

1%

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14
Q

Population Risk - Uterine Cancer

A

3%

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15
Q

Cancer Risk Factors

A
  • age
  • tobacco
  • diet
  • alcohol consumption
  • occupational exposures
  • hereditary factors
  • radiation
  • virus exposure
  • chronic conditions (Crohn’s, celiac)
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16
Q

Colorectal Cancer Risk Factors

A
  • diet
  • family history
  • alcohol
  • cigarettes
  • chronic disease
  • history of polyps
  • older age
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17
Q

Hallmarks of Hereditary Cancer

A
  • cancer diagnosed at an early age (<50; premenopausal)
  • multiple close relatives with same or related cancers
  • 2+ primary cancer diagnoses in same individual
  • certain rare cancers or tumors
  • other features associated with hereditary cancer syndromes
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18
Q

Limitations to Assessing Hereditary Cancer Risk

A
  • small family size/limited family structure
  • incomplete family history
  • inability to document diagnoses
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19
Q

Limited Family Structure

A

fewer than 2 first- or second-degree female relatives surviving beyond age 45 years in either lineage

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20
Q

Uninformative Negative

A
  • negative result in context of undocumented familial pathogenic variant that cannot rule out a hereditary predisposition
  • risk based on personal and family history
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21
Q

True Negative

A
  • negative result in context of a documented and identifiable familial pathogenic variant
  • risk is population risk
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22
Q

Multi-Gene Panel Testing

A
  • benefits: higher mutation detection rate, may reduce uninformative negative results, increased number of patients benefit from risk-reducing options, more cost and time effective than single gene, may reveal more than 1 pathogenic variant
  • limitations: increased chance to find a VUS, variant classifications may differ across labs, limited data regarding cancer risk for some genes, lack of clear guidelines for medical management of mutation carriers for some genes
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23
Q

Polygenic Risk Scores

A
  • combines risk contribution of multiple SNPs to generate a single risk estimate that is more comprehensive than risk estimate obtained from any individual SNPs
  • performance improved when combined with family history or additional clinical features
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24
Q

Breast Anatomy

A
  • 15-20 lobules that produce milk in lactating women
  • fat (1/3 of breast) not considered part of breast tissue
  • stroma is fibrous connective tissue
  • lymphatic system tries to flush out cancer cells when present
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25
Q

Breast Cancer Risk Factors

A
  • age: 1/3 breast cancers in women >50y
  • alcohol use: 2+ drinks per week increase estrogen levels in body
  • benign breast conditions
  • atypical breast cells (hyperplasia)
  • ethnicity: white women more likely to get it; non-white women more likely to die from it
  • personal history and family history
  • hormones: menarche <12y, menopause >55y, ERT, age at first live birth >30y, no pregnancy, no breast-feeding, postmenopausal obesity, prolonged HRT use >5y
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26
Q

Benign Breast Lesions

A
  • cyst: fluid-filled sac; complex cysts should be biopsied
  • fibroadenoma: smooth, round lumps that move easily with breast tissue; size may fluctuate with menstrual cycle
  • microcalcifications: specks of calcium on mammogram; 20% associated with malignant tumor
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27
Q

LCIS

A

not cancer but 7-11x more likely to develop invasive breast cancer

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28
Q

DCIS

A
  • noninvasive, preductal stage 0 breast cancer

- 1/3 turn into invasive cancer

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29
Q

IDC

A
  • 80% of all breast cancer diagnoses
  • originated in epithelial cells of milk duct and spread through duct walls to surrounding tissues
  • types: tubular, medullary (BRCA1), mucinous, colloid, papillary, cribriform
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30
Q

ILC

A
  • 10% of all breast cancer diagnoses
  • originated in lobules and spread through lobule walls to surrounding tissues
  • CDH1/diffuse gastric cancer
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31
Q

Inflammatory Breast Cancer

A
  • 1% of all breast cancer diagnoses

- high-grade, aggressive cancer

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32
Q

Phyllodes Tumor

A
  • “leaf like”
  • originates from stromal cells and may be benign or malignant
  • malignant reported in LFS
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33
Q

Paget’s Disease of the Nipple

A
  • cancer cells collect around nipple causing scaly, red, itchy nipple/areola
  • 97% associated with cancer elsewhere in breast
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34
Q

Breast Cancer Screening - Average Risk

A
  • 25-29y: clinical encounter every 1-3y, breast awareness

- 40y+: annual clinical encounter, annual screening mammo, breast awareness

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35
Q

Women at Increased Risk for Breast Cancer

A
  • prior history of breast cancer
  • women with lifetime risk >20% as defined by models largely based on family history
  • patients who received RT <30y
  • 5-year invasive breast cancer risk >1.7% in women >35y
  • women who have lifetime risk >20% based on history of LCIS or ADH/ALH
  • pedigree suggestive of known genetic predisposition
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36
Q

Breast Cancer Screening - Lifetime Risk >20%

A
  • clinical encounter every 6-12m
  • annual screening mammo, which begins 10y prior to youngest diagnosis but not before 30y
  • recommend annual breast MRI, which begins 10y prior to youngest diagnosis but not before 25y
  • recommend risk-reducing strategies
  • breast awareness
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37
Q

Mammogram

A
  • low dose x-ray picture of breast
  • can detect tumors before palpable
  • less informative in dense breasts
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38
Q

BI-RADS

A
  • breast density levels
  • 40% of women have dense breasts
  • BI-RADS 4-6 require biopsy or treatment
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39
Q

Tomosynthesis

A

3D mammogram

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40
Q

Breast MRI

A
  • uses a powerful magnetic field linked to computer and injection of gadolinium dye for contrast
  • can find things mammo can’t
  • false positives can lead to unnecessary biopsy
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41
Q

Breast Ultrasound

A
  • helps distinguish between fluid-filled cysts from solid tumors
  • offered to women with dense breasts
  • suitable for pregnant women
  • least sensitive and specific
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42
Q

Biopsy

A
  • incisional: takes small sample from mass for analysis
  • excisional: removes entire mass
  • core: removal of tissue using wide needle
  • fine-needle aspiration: removal of tissue using thin needle
  • if malignancy detected, biopsy sentinel lymph node
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43
Q

Cancer Staging

A 
T = size of tumor
N = lymph node involvement
M = metastasis to distant sites
ER = estrogen receptor status
PR = progesterone receptor status
Her2 = her2/neu status
G = cancer grade
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44
Q

OncotypeDx

A
  • 21 gene panel (16 cancer related, 5 reference) performed on breast tumor typically after surgery for ER+, her2-, LN- breast cancers (stage I)
  • predicts likelihood of recurrence and likely benefit of addition of adjuvant systemic chemotherapy to adjuvant endocrine therapy
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45
Q

Lumpectomy

A

partial mastectomy or breast-conserving surgery

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46
Q

Mastectomy

A
  • modified radical: removes breast, most/all lymph nodes, lining over chest muscles
  • radical: also removes pectoral muscles
  • total/simple: leaves behind lymph nodes and muscles
  • double: both breasts
  • skin sparing: for immediate breast reconstruction
  • nipple sparing: nipple and areola left intact
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47
Q

Breast Reconstruction

A
  • implant reconstruction: saline, silicone gel, or combo

- autologous/flap reconstruction: tissue transplanted from another part of body

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48
Q

Radiation

A

targets remaining breast tissue, neighboring lymph nodes, chest wall via external beams or surgically implanted seeds

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49
Q

Chemotherapy

A

post-op systemic therapy or neoadjuvant therapy (treat tumor before surgery)

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50
Q

Hormonal Therapy

A
  • ER/PR+: tamoxifen, aromatase inhibitor (good for postmenopausal women)
  • Her2+: Herceptin, Perjecta
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51
Q

PARP Inhibitor

A
  • biological therapy that prevents PARP from repairing double-stranded breaks
  • BRCA genes repair DNA through homologous recombination while PARP repairs through base excision repair
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52
Q

Candidates for Breast Cancer Counseling

A
  • early age of onset
  • multiple relatives with same/related cancer
  • multiple promaries
  • AJ ancestry
  • unusual presentation/rare cancer
  • pathology (TNBC)
  • known pathogenic variant, including those uncovered on tumor testing
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53
Q

Gail Model

A
  • only used for women 35-85y
  • estimates risk of developing invasive breast cancer over next 5 years and up to age 90
  • uses personal medical and reproductive history along with history of breast cancer in 1st degree relatives
  • validated for many ethnicities
  • should not be used for women with hereditary cancer syndrome, extensive family history beyond first degree relatives, received radiation, previous history of breast cancer
  • can underestimate hereditary risk of breask cancer
  • 5y risk >1.7% indicates qualification for tamoxifen
54
Q

Tyrer-Cuzick Model

A
  • used for women 20-85y without a personal history of breast cancer
  • estimates 10y and lifetime risk for cancer as well as BRCA risk
  • based on UK population, so not as accurate for non-white populations
  • adjusts for negative BRCA results, can include cousins, adjusts for AJ ancestry
  • incorporates menarche, parity, age of first child, age at menopause, use of HRT, atypical hyperplasia, LCIS, premenopausal height, postmenopausal BMI
  • places emphasis on biopsy history which may inflate risks, no inclusion of male prostate or pancreatic cancers
55
Q

Claus Model

A
  • statistical model used to calculate cumulative breast cancer risk based on family history (only factor considered)
  • incorporates age at diagnosis, cumulative risk by age, paternal relatives, second degree relatives
  • best for moderate risk patients, may underestimate risk in families with 3+ affected relatives, and does not take into account lifestyle factors
56
Q

Myriad Tables

A
  • two tables, one for AJ and one for non-AJ individuals based on personal history, family history/degree of relationship to breast or ovarian cancers
  • predicts BRCA1/2 mutations
57
Q

BRCAPro

A
  • predicts BRCA1/2 mutations and breast and ovarian cancer risks based on BRCA1/2 risks
  • includes unaffected family members to modify risk, male breast cancers, age of diagnosis
  • includes adjustment based on pathological features/biomarkers of patient’s cancer, genetic testing results, history of oophorectomy, risks of other BRCA-associated cancers, race, penetrance estimates
58
Q

Pen II Model

A
  • pretest probability of BRCA1/2
  • does not predict breast cancer risk
  • one lineage at a time, does not combine maternal and paternal history
  • accounts for prostate and pancreatic cancer
59
Q

BOADICEA

A
  • accounts for current age/age of death, year of birth (cohort effect), age of diagnosis, occurrence/lack of for survivors, genetic testing results, half sibs, male breast cancer, pancreatic cancer, prostate cancer, AJ ancestry, genes other than BRCA1/2
  • often requires info not available, does not account for non-genetic factors, does not adjust for pathology, does not include previous oophorectomy, underestimates mutation detection rate, “research use only”
60
Q

Cleveland Clinic PTEN Calculator

A

calculates risk for having PTEN mutation

61
Q

AJ Founder Mutations

A

c. 68_69delAG or 187delAG
c. 5266dupC or 5382insC
c. 5946delT or 6174delT

62
Q

PALB2

A
  • 17-58% breast cancer risk
  • risk for pancreatic cancer, male breast cancer, Fanconi anemia
  • screening: annual mammo, consider breast MRI with contrast at 30y
63
Q

CHEK2

A
  • 23-48% (variant specific) breast cancer risk
  • risk for CRC, male breast cancer
  • screening: annual mammo, consider breast MRI with contrast at 40y
64
Q

ATM

A
  • 17-52% breast cancer risk
  • risk for pancreatic, prostate, maybe ovarian cancers, ataxia telangiectasia
  • screening: annual mammo, consider breast MRI with contrast at 40y
65
Q

NBN

A
  • up to 30% breast cancer risk
  • risk for prostate cancer, Nijmegen breakage syndrome
  • screening: annual mammo, consider breast MRI with contrast at 40y
66
Q

NF1

A
  • 8.4% breast cancer risk to age 50 compared with gen pop of 1.9%
  • risk for neurofibromas, GIST, malignant peripheral nerve sheath tumors
  • screening: annual mammo at 30y, consider breast MRI with contrast 30-50y
67
Q

BARD1

A
  • potentially increased breast cancer risk
68
Q

BRCA1 Cancer Risks

A
  • breast: 50-85%
  • second breast primary: 13-20%
  • ovarian: 20-44%
  • male breast: 1-2%
  • prostate: elevated
  • pancreatic: elevated
69
Q

BRCA2 Cancer Risks

A
  • breast: 40-70%
  • second breast primary: 8-12%
  • ovarian: 15-27%
  • male breast: 7%
  • prostate: 20%
  • pancreatic: 2-7%
  • melanoma: elevated
70
Q

Mutation Positive Management Recommendations - Breast Cancer

A
  • increased surveillance: breast MRI with contrast 25-29y, annual mammo + breast MRI 30-75y
  • prophylactic surgery: risk-reducing mastectomy, BSO (35-40y for BRCA1, 40-45y in BRCA2)
  • chemoprevention: tamoxifen (ER+, BRCA2, premenopausal), aromatase inhibitors (postmenopausal)
  • PARP inhibitors
71
Q

Gynecologic Anatomy

A
  • ovary: produces oocytes
  • fallopian tube: transports oocytes to site of fertilization
  • uterus: promotes implantation of fertilized egg in uterine wall, otherwise menstruation occurs
  • FSH, LH, estrogen, and progesterone produced to maintain reproductive cycles and promote bone density
  • peritoneum: serous membrane lining abdominal cavity and surrounding organs
  • lymphatic system: drainage system that can enable metastasis of cancer cells
  • 95% of uterine cancers are endometrial
72
Q

Risk Factors for Uterine Cancer

A
  • age >50y
  • endometrial hyperplasia
  • estrogen exposure: estrogen-only HRT, early menstruation, late menopause, never being pregnant, obesity (6x higher risk), diabetes, tamoxifen in postmenopausal women
  • previous pelvic radiation
  • family history in FDR
  • hereditary cancer syndrome
  • Caucasian ethnicity
  • cigarettes are protective
73
Q

Risk Factors for Ovarian Cancer

A
  • family history in FDR (5% lifetime risk)
  • hereditary cancer syndrome
  • age (rare <40y)
  • obesity
  • estrogen-only HRT after menopause
  • North American, Northern European, or AJ heritage
  • pregnancy, breastfeeding, oral contraceptives protective
74
Q

Risk Factors for Vaginal Cancer

A
  • age
  • HPV
  • smoking
  • cervical cancer
  • previous radiation
  • diethystilbestrol (DES) exposure
75
Q

Risk Factors for Cervical Cancer

A
  • age (late teens - mid 30’s)
  • HPV, herpes
  • smoking
  • immune system deficiency
  • DES exposure
  • socioeconomic factors
76
Q

Noncancerous Uterine Lesions

A
  • fibroids/leiomyomas: benign tumors in uterine muscle
  • benign polyps
  • endometriosis: endometrial tissue found outside of uterus
  • endometrial hyperplasia: increased number of cells and glandular structures in uterine lining
77
Q

Types of Uterine Cancer

A
  • endometrial cancer/adenocarcinoma (85-95%): type I have endometrioid histology and associated with PTEN, type II have non-endometrioid histology and have poorer prognosis
  • sarcoma (<5%): leiomyosarcoma, endometrial stromal sarcoma
78
Q

Types of Ovarian Cancer

A
  • epithelial (majority): benign, borderline, malignant (85-90% of malignant ovarian tumors; serous, endometrioid, clear cell, mucinous)
  • germ cell (benign): develops in egg-producing cells of ovaries; 10-29y
  • stromal: connective tissue tumors; associated with PJS
  • cyst
79
Q

Signs/Symptoms of Uterine Cancer

A
  • unusual vaginal bleeding/discharge
  • pelvic pain
  • pain during intercourse
  • difficult/painful urination- abnormal Pap
80
Q

Diagnosis of Uterine Cancer

A
  • physical exam of pelvis
  • medical history
  • endometrial biopsy
  • dilation and curettage
  • imaging: hysteroscopy, transvaginal u/s, CT, MRI
81
Q

Treatment of Uterine Cancer

A
  • surgery: vaginal hysterectomy, TAH, total laparoscopic hysterectomy
  • radiation, chemotherapy, hormone therapy/biological therapy
82
Q

Signs/Symptoms of Ovarian Cancer

A
  • pain, swelling, pressure in abdomen/pelvis
  • irregular/heavy vaginal bleeding, especially after menopause
  • vaginal discharge
  • lump in pelvic area
  • GI problems
  • ascites
83
Q

Diagnosis of Ovarian Cancer

A
  • physical exam of pelvis
  • medical history
  • CA-125 assay
  • biopsy or paracentesis (removal of ascites fluid)
  • imaging: transvaginal or abdominal u/s, CT, PET, MRI, chest x-ray
84
Q

Favorable Prognostic Factors for Ovarian Cancer

A
  • younger age
  • cell type other than mucinous or clear cell
  • grade 1 tumor/early disease
  • absence of ascites
  • lower disease volume before surgical debulking
  • smaller residual tumor after primary cytoreductive surgery
  • BRCA carrier (platinum based chemo, PARP)
85
Q

Treatment of Ovarian Cancer

A
  • surgery: salpingo-oophorectomy, hysterectomy, lymphadenectomy/lymph node dissection, omentectomy, cytoreductive/debulking surgery
  • chemotherapy, targeted therapy, radiation, immunotherapy, clinical trial
  • oncofertility preservation
86
Q

Risk Factors for Prostate Cancer

A
  • age >65y
  • race/ethnicity: black men have a higher risk and tends to be more aggressive
  • family history: risk is 2-3x high in men with affected FDR
  • hereditary cancer syndrome (BRCA2)
87
Q

Prostate Cancer Screening

A

digital rectal exam or PSA blood test starting at 45y

88
Q

Gleason Score

A
  • used to grade prostate cancer
  • score assigned from 3-5 based on two locations and added together
  • scores 7+ concerning and warrant genetic testing
89
Q

Treatment of Prostate Cancer

A
  • watchful waiting/surveillance
  • radiation
  • surgery
90
Q

Testicular Cancer

A
  • typically germ cell tumors
  • lifetime risk <1%
  • average age at diagnosis is 33y
  • risk factors: age (20-45y), cryptorchidism, personal/family history, race (more common in white men), HIV
  • no screening
  • treatment includes radiation, chemo, surgery
91
Q

BRIP1

A
  • 5.8% ovarian cancer risk
  • risk for Fanconi anemia
  • consider RRSO 45-50y
92
Q

RAD51C

A
  • 6.7% ovarian cancer risk
  • risk for Fanconi anemia
  • consider RRSO 45-50y
93
Q

RAD51D

A
  • 14.8% ovarian cancer risk

- consider RRSO 45-50y

94
Q

Colon Anatomy

A

cecum (right-sided) -> ascending colon -> hepatic flexure -> transverse colon -> splenic flexure -> descending colon (left-sided) -> sigmoid colon -> rectum -> anus

95
Q

Screening Options for CRC

A
  • colonoscopy: gold standard; prep required, procedure done under anesthesia
  • fecal occult blood test: noninvasive/inexpensive/private; positive result indicates cancer already present
  • CTC colonoscopy (virtual): prep required, gas inserted through rectal tube; needs to be followed up with normal colonoscopy if suspicious findings present
  • flexible sigmoidoscopy
96
Q

Screening for CRC - Average Risk

A
  • starting at age 50
  • every 10y if no polyps found
  • FOBT yearly
  • CTC colonoscopy every 5y
  • flexible sigmoidoscopy every 5-10y
97
Q

Screening for CRC - Increased Risk

A
  • 1+ FDR with CRC: colonoscopy beginning at age 40y or 10y prior to youngest diagnosis; repeat every 5y if negative
  • 1+ SDR with CRC <50: colonoscopy beginning at age 50y; repeat every 5-10y if negative
  • FDR with advanced adenomas: colonoscopy beginning at 40y or at age of onset of adenoma; repeat every 5-10y if negative
98
Q

MSI

A
  • accounts for 15% of cases of CRC (85% due to chromosomal instability)
  • short, repetitive DNA sequences found throughout tumor genome that are prone to mutations leading to frameshifts
  • cancers with MSI tend to be right-sided (sporadic are left-sided), have higher numbers of lymphocytes, improved survivability
99
Q

IHC

A

looks for presence/absence of MLH1, MSH2, MSH6, and PMS2 proteins on tumor tissue

100
Q

MLH1 Promoter Methylation

A

hypermethylation pathway that involves CpG islands and tends to be sporadic

101
Q

BRAF

A
  • V600E mutation seen in 8-11% of all CRC tumors and 80% of all MLH1-deficient tumors
  • presence indicates sporadic MSI CRC and excludes diagnosis of Lynch
102
Q

CRC Prediction Models

A
  • MMRPro, MMRPredict, PREMM5

- consider testing for Lynch syndrome if predicted risk score >5% on prediction model

103
Q

Types of Colon Polyps

A
  • pedunculated tubular adenoma (FAP)
  • hamartoma (PJS, JPS)
  • hyperplastic/serrated adenoma (SPS)
  • inflammatory (celiac, Crohn’s, IBS)
104
Q

Detection of Polyps

A
  • colonoscopy (if >10 adenomatous polyps over lifetime, genetic evaluation necessary)
  • rectal bleeding
  • anemia on CBC
  • diarrhea/constipation/”change in bowel habits”
105
Q

MLH1/MSH2 Cancer Risks

A
  • colon: 52-82%
  • endometrium: 25-60%
  • ovarian: 11-20% for MLH1, 15-24% for MSH2
  • prostate: 30%
  • stomach: 6-13%
  • other cancer risks: hepatobiliary tract, urinary tract, small bowel, brain/CNS, sebaceous neoplasms, pancreas
106
Q

MSH6 Cancer Risks

A
  • colon: 10-22%
  • endometrium: 16-26%
  • prostate: 30%
  • stomach: 3% or less
107
Q

PMS2 Cancer Risks

A
  • colon: 15-20%
  • endometrium: 15%
  • CMMRD
108
Q

Hereditary Breast Cancer Syndromes

A
  • BRCA1/2
  • PALB2, CHEK2, ATM, NBN, NF1, BARD1
  • Li Fraumeni Syndrome
  • Hereditary Diffuse Gastric Cancer Syndrome
  • PTEN/Cowden
  • PJS
109
Q

Hereditary GYN Cancer Syndromes

A
  • BRCA1/2
  • Lynch Syndrome
  • BRIP1, RAD51C, RAD51D
  • PJS
  • PTEN/Cowden
  • HLRCC
110
Q

Hereditary CRC Syndromes

A
  • Lynch Syndrome
  • FAP
  • AFAP
  • MUTYH-Associated Polyposis
  • MSH3-Associated Polyposis (FAP4)
  • GREM1
  • NTHL1-Associated Polyposis
  • Polymerase Proofreading Associated Polyposis
  • PTEN/Cowden
  • PJS
  • JPS
  • Serrated Polyposis Syndrome
111
Q

Hereditary Neuroendocrine Cancer Syndromes

A
  • MEN1
  • MEN2 (A, B, FMTC)
  • MEN4
  • Hereditary Paraganglioma/Pheochromocytoma Syndrome
  • von Hippel Lindau
112
Q

Hereditary Renal Cancer Syndromes

A
  • von Hippel Lindau
  • Birt-Hogg-Dube
  • HLRCC
  • Hereditary Papillary Renal Carcinoma
113
Q

Hereditary Dermatologic Cancer Syndromes

A
  • Familial Atypical Multiple Mole Melanoma
  • Nevoid Basal Cell Carcinoma/Gorlin
  • Xeroderma Pigmentosum
114
Q

Hereditary CNS Cancer Syndromes

A
  • NF1
  • NF2
  • Tuberous Sclerosis
115
Q

Hereditary Pediatric Cancer Syndromes

A
  • 65% of pediatric cancers in general are leukemias, lymphomas, and brain/CNS tumors
  • Li Fraumeni Syndrome
  • Hereditary Retinoblastoma
  • Hereditary Neuroblastoma
  • Fanconi anemia
  • DICER1 Syndrome
  • Gorlin Syndrome
  • Hereditary Predisposition to AML/ALL
  • Tuberous sclerosis
  • FAP
  • MEN2
  • DNA instability syndromes: Bloom, CMMRD, ataxia telangiectasia, xeroderma pigmentosum, NBS, Diamond-Blackfan anemia, dyskeratosis congenita
116
Q

Testing Criteria for Breast, Ovarian, Prostate and Pancreatic Cancers

A
  • blood relative with a known P/LP variant
  • meet criteria and previous limited testing
  • personal history of breast cancer <45y, 46-50y with limited fhx/second primary/1+ close relative with related cancer, <60y with TNBC, any age with AJ ancestry, any age with 1+ close relative with related cancer (breast <50y), any age with 3+ breast cancer diagnoses in patient/close relatives, male breast cancer at any age
  • epithelial ovarian cancer at any age
  • exocrine pancreatic cancer at any age
  • metastatic or intraductal prostate cancer at any age
  • Gleason 7+ and AJ ancestry, or 1+ close relative with related cancer (breast <50y), or 2+ close relatives with breast/prostate cancer
  • mutation identified on tumor testing
  • affected/unaffected individual with FDR/SDR meeting criteria
  • affected/unaffected individual who does not meet criteria but has probability >5% for BRCA1/2 mutation
117
Q

Testing for LFS

A
  • Classic Criteria: individual diagnosed <45y with sarcoma, FDR diagnosed <45y with cancer, and additional FDR/SDR in same lineage with cancer <45y or sarcoma at any age
  • Chompret Criteria: individual with LFS tumor <46y and 1 FDR/SDR with LFS tumor <56y or multiple primaries at any age; individual with multiple tumors belonging to LFS spectrum with initial tumor <46y; individual with ACC or choroid plexus carcinoma or rhabdomyosarcoma at any age; breast cancer <31y
  • known P/LP variant
  • mutation identified on tumor testing
118
Q

Testing for Cowden/PTEN

A
  • known P/LP variant
  • personal history of Bannayan-Riley-Ruvalcaba
  • meeting clinical diagnostic criteria: Lhermitte-Duclos, ASD + macrocephaly, 2+ trichilemmomas, 2+ major criteria (w/ macrocephaly), 3 major criteria (w/o macrocephaly), 1 major and 3+ minor criteria, 4+ minor criteria
  • mutation identified on tumor testing
119
Q

Testing for Lynch Syndrome

A
  • known P/LP variant
  • personal history of CRC/endometrial at any age with positive IHC/MSI; CRC/endometrial cancer <50y, or synchronous/metachronous LS-related cancer, or 1+ FDR/SDR with LS cancer <50y, or 2+ FDR/SDR with LS cancer at any age; CRC tumor with MSI-H histology
  • family history of 1+ FDR with CRC/endometrial cancer <50y; 1+ FDR with CRC/endometrial cancer and another LS cancer; 2+ FDR/SDR with LS cancer with one <50y; 3+ FDR/SDR with LS cancer at any age
  • 5% + risk of having MMR mutation based on models
  • meeting Amsterdam II or Bethesda guidelines
120
Q

Amsterdam II (3-2-1 rule)

A
  • 3+ relatives with LS-associated cancers (1 must be FDR of other two)
  • at least 2 successive generations affected
  • at least 1 diagnosed <50y
  • FAP excluded
121
Q

Bethesda

A
  • CRC <50y
  • synchronous or metachronous LS cancer at any age
  • CRC with MSI-H histology <60y
  • CRC and 1+ FDR with LS cancer <50y
  • CRC and 2+ FDR/SDR with LS cancer at any age
122
Q

Testing for Adenomatous Polyposis

A
  • personal history of 20+ cumulative adenomas
  • known P/LP variant
  • consider testing if personal history of desmoid tumor, hepatoblastoma, cribriform-morular variant of papillary thyroid cancer, CHRPE, criteria met for SPS, 11-20 cumulative adenomas
123
Q

Testing for Peutz-Jeghers Syndrome

A
  • clinical diagnosis made when individual has 2+ of: 2+ PJ-type hamartomatous polyps, mucocutaneous pigmentation, family history of PJS
124
Q

Testing for Juvenile Polyposis Syndrome

A
  • clinical diagnosis made when individual has 1 of: 5+ juvenile polyps, multiple juvenile polyps throughout GI tract, any juvenile polyps when there’s a family history of JPS
  • genetic testing recommended
  • if known SMAD4 variant, genetic testing should be performed within first 6mos of life due to HHT risk
125
Q

Testing for Serrated Polyposis Syndrome

A
  • RNF43 gene; otherwise no causative gene identifiable
126
Q

Individuals Eligible for Screening for Pancreatic Cancer

A
  • known P/LP variants in ATM, BRCA1/2, CDKN2A, MLH1, MSH2, MSH6, EPCAM, PALB2, STK11, TP53 and family history of pancreatic cancer in FDR/SDR from same side of family as germline variant
  • family history of exocrine pancreatic cancer in 2+ FDR from same side of family
  • family history of exocrine pancreatic cancer in 3+ FDR/SDR from same side of family
127
Q

Screening Methods for Pancreatic Cancer

A
  • contrast-enhanced MRI/magnetic resonance cholangiopancreatography (MRCP)
  • endoscopic ultrasound
  • usually done under research conditions
128
Q

Pancreatic Cancer Screening - STK11

A

screening starting 30-35y or 10y prior to youngest diagnosis

129
Q

Pancreatic Cancer Screening - CDKN2A

A

screening starting 40y or 10y prior to youngest diagnosis

130
Q

Pancreatic Cancer Screening - Mutation in Another Susceptibility Gene

A
  • screening starting 50y or 10y prior to youngest diagnosis for individuals with exocrine pancreatic cancer in 1+ FDR/SDR from same side of family as germline variant
  • not recommended in absence of family history

Genetic Counseling Boards (22 decks)

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