Cancer

HBOC

• BRCA1 / BRCA2

• AD

• Breast, Ovarian, Pancreatic, Prostate, Skin

• BRCA1 worse breast, ovarian. BRCA2 worse pancreatic, skin. Triple negative breast. Biallelic Fanconi anemia

BOPPS - B (Breast), O (Ovarian), P (Pancreatic), P (Prostate), S (Skin)

Ataxia Telangiectasia

• ATM

• AD / AR

• Breast, Ovarian, Pancreatic, Prostate mono. Ataxia, telangiectasa, leukemi bi

• Monoallelic causes cancer, biallelic causes movement

AT LASK - A (Ataxia), T (Telangiectasia), L (Leukemia), A (Adult-Onset Breast , Ovarian, Pancreatic Prostate Cancers), S (Sensitive to Radiation), K (Klumsy Movement)

Ataxia Telangiectasia

• ATM

• AD / AR

• Breast, Ovarian, Pancreatic, Prostate mono. Ataxia, telangiectasa, leukemi bi

• Monoallelic causes cancer, biallelic causes movement

AT LASK - A (Ataxia), T (Telangiectasia), L (Leukemia), A (Adult-Onset Breast , Ovarian, Pancreatic Prostate Cancers), S (Sensitive to Radiation), K (Klumsy Movement)

PALB2

• PALB2

• AD

• Breast, Ovarian, Pancreatic, Prostate

• bridges BRCA1/2 (PAL that Bridges BRCA1/2)

POM - P (Pancreatic), B (Breast Cancer), O (Ovarian Cancer), M (Male Prostate)

RAD51C

• RAD51C

• AD/ AR

• Breast, Ovarian, Fanconi Anemia (Leukemia, Skeletal)

• Mono-allelic causes cancer, biallelic causes fanconi anemia

RAD FAN - R (Risk for Ovarian Cancer), A (Adult Onset Breast Cancer), D (Deformed Thumbs and Radius), F (Failure of Bone Marrow), A (Abnormal Pigmentation), N (Neoplasm Risk

RAD51D

• RAD51D

• AD

• Breast, Ovarian

OBN - O (Ovarian Cancer Risk), B (Breast Cancer Risk), N (No Fanconi Anemia Risk)

BRIP1

• BRIP1

• AD

• Ovarian, Fanconi Anemia (Leukemia, Skeletal)

• Monoallelic causes cancer, biallelic causes fanconi anemia

BRIPL - B (Biallelic Bone Marrow Failure), R (Risk of Ovarian Cancer), I (Insignificant Breast Cancer Risk), P (Physical Congenital Anomalies), L (Leukemia)

Lynch Syndrome

• MLH1 = MSH2, PMS2 = MSH6 / EPCAM

• AD / AR

• Colorectal Cancer, Endometrial Cancer, Gastric Cancer, Ovarian Cancer

• Monoallelic causes cancer (Turcot / Muir-Torre Variants), Biallelic causes CMMRD

CEO SGU - C (Colorectal), E (Endometrial), O (Ovarian), S (Stomach), G (Gallbladder / Pancreatic), U (Urinary)

Turcot

• MLH1 = MSH2, PMS2 = MSH6 / EPCAM, APC

• AD

• Colorectal Cancer, Endometrial Cancer, Gastric Cancer, Ovarian Cancer, Brain Cancer

• Caused by Lynch syndrome genes or FAP genes

MAPS - M (Medulloblastoma), A (Astrocytoma / Glioblastoma Multiforme), P (Polyposis), S (Skin Changes, Cafe-au-lait)

Muirr-Torre

• MSH2, MLH1 or MSH6

• AD

• Colorectal Cancer, Endometrial Cancer, Gastric Cancer, Ovarian Cancer, Skin Cancer

MS - M (MMR cancers), S (Skin cancer)

CMMRD

• MLH1 = MSH2, PMS2 = MSH6

• AR

• Very Early Colorectal Cancer, Cafe-au-lait spots, Brain Cancer, Gastric Cancer, Pancreatic Cancer

CCCC - C (Central Nervous System / Brain Tumors), C (Colon Cancer), C (Cafe-au-lait spots), C (Caused Early)

FAP

• APC

• AD

• 1000s of polyps, almost 100% Colorectal cancer, Gastric cancer, Thyroid Cancer, CHRPE, Osteomas

CARPET - C (CHRPE), A (Adenomas), R (Risk of Duodenal / Gastric Cancers), P (Prophylatic Colectomy Required), E (Epidermal Cysts), T (Thyroid Cancers)

AFAP

• APC

• AD

• Colorectal cancer, Gastric cancer,

• 100s of polyps

SPAE - S (Sparing of CHRPE), P (Polyps but less), A (Age of onset is Delayed), E (Elevated Colorectal Cancer Risk)

MUTYH-Associated Polyposis

• MUTYH

• AR

• Colorectal cancer, Gastric cancer, Duodenal Polyposis

• Similar to AFAP, 100s of polyps

MEC – M (Milder/Attenuated Polyposis presentation), E (Extra-colonic benign signs), C (Carcinomas of the Endometrium, Colon, Thyroid and Ovary)

Juvenline Polyposis syndrome

• SMAD4, BMPR1A

• AD

• Colorectal cancer, Gastric Cancer, Pancreatic Cancer

JUV - J (Juvenile polyps (hamartomas with dilated mucus glands), U (Upper & lower GI cancers (colorectal and stomach), V (Vascular anomalies (if SMAD4 is mutated, adding a risk for nosebleeds and internal blood vessel malformations).

Hereditary nonpolyp colon cancer

• MLH1, MSH2, MSH6, PMS2, EPCAM

• AD

• Colorectal cancer, Endometrial cancer, Gastric cancer, Ovarian cancer, Urothelial cancer

• Synonymous with Lynch Syndrome. Characterized by microsatellite instability (MSI-H).

Peutz-Jehgers

• STK11

• AD

• Gastrointestinal hamartomatous polyps, mucocutaneous hyperpigmentation (melanocytic macules on lips/buccal mucosa). High breast, pancreatic, and GI cancer risks.

PACH - P (Pigmentation on lips), A (Adenocarcinoma risks: Breast/GI), C (Cervical/Ovarian rare tumors), H (Hamartomatous polyps)

Polymerase proofreading ass. Polyposis

• POLE, POLD1

• AD

• Multiple adenomatous polyps (attenuated or classic count), early-onset colorectal cancer, endometrial cancer

• POLE - P (Polyposis/Polymerase), O (Onset is early), L (Lynch-like endometrial risk), E (Exonuclease proofreading defect)

Gardner syndrome

• APC

• AD

• Colorectal polyposis, osteomas (jaw/skull), desmoid tumors, epidermoid cysts, Extra (supernumerary) teeth

PODS - P (Polyps), O (Osteomas), D (Desmoid tumors), S (Skin cysts / Supernumerary teeth)

CDH1

• CDH1, CTNNA1

• AD

• Diffuse gastric cancer (linitis plastica, signet ring cells), lobular breast cancer, cleft lip/palate.

DIFFUSE - D (Diffuse gastric cancer), I (Invisibly infiltrating signet ring cells), F (Frustrated screening/total gastrectomy), F (Female lobular breast cancer), U (Unexpected cleft lip/palate), S (Stomach wall thickening), E (Early onset)

CDKN2A

• CDKN2A

• AD

• Cutaneous malignant melanoma, pancreatic cancer.

PM - P (Pancreatic cancer), M (Melanoma)

Gorlin syndrome

• PTCH1, SUFU

• AD

• Basal cell carcinomas (BCCs), odontogenic keratocysts (OKCs) of jaw, palmar/plantar pits, calcification of falx cerebri, medulloblastoma.

BASE - B (Basal cell carcinomas), A (Anomalies of skeleton/falx calcification), S (SUFU/PTCH1 genes), E (Epithelial keratocysts of the jaw)

Von-Hippel Lindau

• VHL

• AD

• Clear cell renal cell carcinoma (RCC), CNS and retinal hemangioblastomas, pheochromocytomas, endolymphatic sac tumors, pancreatic cysts.

HRP - H (Hemangioblastomas), R (Renal cell carcinoma - clear cell), P (Pheochromocytoma / Pancreatic NETs)

Hereditary Leiomyomatosis and RCC

• FH

• AD / AR

• Cutaneous leiomyomas (painful skin bumps), uterine leiomyomas (severe fibroids), aggressive type 2 papillary renal cell carcinoma.

• Fumarate Hydratase. Biallelic mutations cause severe metabolic/neurological Fumarase Deficiency.

ULC - U (Uterine fibroids/leiomyomas), L (Leiomyomas of skin), C (Carcinoma of the kidney - aggressive papillary type 2)

Birt-Hogg-Dube

• FLCN

• AD

• Skin fibrofolliculomas, lung cysts, spontaneous pneumothorax, chromophobe RCC or hybrid oncocytic tumors (HOCT).

BLOBS - B (Benign skin fibrofolliculomas), L (Lung cysts), O (Oncocytic/chromophobe RCC), B (Burst lung/spontaneous pneumothorax), S (Surveillance with MRI)

Serrated polyposis syndrome

• RNF43 rare

• Variable / Sporadic

• Serrated polyps (hyperplastic and sessile serrated), Colon Cancer

WHO - W (WHO diagnostic criteria), H (Hyperplastic and sessile serrated polyps), O (Oncogenic risk for CRC)

MEN1

• MEN1

• AD

• Parathyroid adenomas (hyperparathyroidism), Pituitary adenomas (prolactinomas), Pancreatic neuroendocrine tumors (gastrinomas/insulinomas).

PPP - P (Parathyroid), P (Pituitary), P (Pancreatic NETs)

MEN2

• MEN2

• RET

• AD

• Medullary thyroid carcinoma (MTC), pheochromocytoma. MEN2A: adds hyperparathyroidism. MEN2B: adds mucosal neuromas, marfanoid habitus.

MPH - M (Medullary thyroid carcinoma), P (Pheochromocytoma), H (Hyperparathyroidism for MEN2A / Mucosal neuromas for MEN2B)

Hered. Paraganglioma/pheo

• SDHA, SDHB, SDHC, SDHD, SDHAF2

• AD

• Paragangliomas (head/neck or extra-adrenal) and Pheochromocytomas. Gastrointestinal stromal tumors (GIST), clear cell RCC.

ULK - U (Uterine fibroids/leiomyomas), L (Leiomyomas of skin), K (Kidney Carcinoma- aggressive papillary type 2)

PTEN hamartoma syndrome

• PTEN

• AD

• Macrocephaly, trichilemmomas, papillomatous papules, hamartomatous GI polyps, Lhermitte-Duclos disease, high risk of breast, thyroid (follicular), endometrial, and renal cancers.

PTEN - P (Papules/Papillomas/Polyps), T (Thyroid/Breast/Endometrial cancer), E (Early macrocephaly), N (Neurological Lhermitte-Duclos)

Cowden

• PTEN

• AD

• Breast cancer, follicular thyroid cancer, endometrial cancer

• Late-adolescent/adult onset. Trichilemmomas, papillomas, macrocephaly, Lhermitte-Duclos disease (cerebellar hamartomas).

TOP - T (Trichilemmomas), O (Oversized Head), B (Breast, Follicular Thyroid, and Endometrial cancers)

Bannayan-Riley-Ruvalcaba Syndrome

• PTEN

• AD

• Pediatric onset. Macrocephaly, penile lentigines, multiple subcutaneous lipomas, hemangiomas, developmental delay.

• Cancer in adulthood, breast, follicular thyroid, endometrial

SPOT - S (Subcutaneous Lipomas & Hemangiomas), P (Penile Lentigines), O (Onset in Childhood), T (Tumor Risks (Shared)

PTEN-Related Proteus Syndrome (PS)

• PTEN

• AD

• Congenital/infantile onset. Severe, asymmetric, progressive overgrowth of limbs/organs, cerebriform connective tissue nevi (thick skin on soles/palms), vascular malformations.

• Shared lifetime PHTS cancer risks, breast, follicular thyroid, endometrial

LIMB - L (Limb Asymmetry), I (Infiltrating Lipomas & Vascular Malformations), M (Mosaicism Mimic), B (Bottom of Foot Nevi)

PTEN-Related Proteus-Like Syndrome

• PTEN

• AD

• Overlapping features of Proteus syndrome (asymmetric overgrowth) but fails to meet the full formal clinical diagnostic criteria for true Proteus syndrome.

• Shared lifetime PHTS cancer risks, breast, follicular thyroid, endometrial

NEAR - N (Not Fully Meeting Criteria), E (Exhibits Complex Overlap, Cowden and Proteus), A (Asymmetric Overgrowth Present), R (Requires Same Surveillance:)

Xeroderma pigmentosum

• XPA, XPC, ERCC2, etc.

• AR

• Extreme UV sensitivity, severe sunburns, heavy freckling in sun-exposed skin, 10,000x increased risk for skin cancers (BCC, SCC, melanoma), corneal scarring.

• UV - U (Ultra-sensitive to sun), V (Vast increase in skin cancers)

Carney Complex

• PRKAR1A

• AD

• Cardiac myxomas, cutaneous myxomas, spotty skin pigmentation (lentigines), primary pigmented nodular adrenocortical disease (PPNAD / Cushing syndrome), pituitary adenomas.

SPOT - S (Spotty skin pigmentation), P (Pituitary and endocrine tumors), O (Overproducing cortisol), T (The cardiac myxomas)

Li-Fraumeni

• TP53

• AD

• Sarcomas (osteosarcoma and soft tissue), early-onset Breast cancer, Brain tumors, Adrenocortical carcinoma (ACC), Leukemia.

SBLA - S (Sarcoma), B (Breast), L (Leukemia/Lymphoma), A (Adrenocortical carcinoma / Brain)

Thyroid

• FOXE1, HABP2, etc.

• AD

• Familial non-medullary thyroid carcinoma (papillary, follicular) or medullary thyroid carcinoma depending on sub-type.

THY - T (Thyroid nodules), H (Hereditary forms), Y (Young age of onset)

Retinoblastoma

• RB1

• AD

• Leukocoria (white pupil reflex), strabismus, unilateral or bilateral retinoblastoma in infancy/early childhood. Increased adult risk for osteosarcoma and melanoma.

RB - R (Retinal tumor / white Reflex), B (Bilateral often / Bone osteosarcoma later)

Fanconi anemia

• FANCA, FANCC, FANCD2, BRCA2, PALB2, RAD51C, BRIP1, etc.

• AR / XL

• Progressive bone marrow failure (aplastic anemia), radial ray defects (absent/deformed thumbs), short stature, café-au-lait spots, high pediatric AML risk.

FANC- F (Failure of bone marrow), A (Anomalies of radius/thumbs), N (Neoplasms: AML/Squamous cell), C (Cafe-au-lait spots / Chromosome breaks)

Nijmegen breakage syndrome

• NBN

• AR

• Progressive microcephaly, bird-like facies, severe immunodeficiency (recurrent respiratory infections), radiosensitivity, high risk for B-cell lymphoma.

NBN - N (Nibrin gene/No head size/Microcephaly), B (Bird-like facies / B-cell lymphoma), N (Not resistant to radiation/Radiosensitive)

Bloom syndrome

• BLM

• AR

• Severe proportional growth deficiency (short stature), sun-sensitive butterfly rash on face, immunodeficiency, high risk of early-onset malignancies across all types.

BLM - B (Butterfly rash / Bloom helicase), L (Little stature / Low immunity), M (Malignancies of all types)

Ataxia-telangiectasia

• ATM

• AR

• Progressive cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, lymphoid malignancies, extreme radiosensitivity.

AT MASK - A (Ataxia), T (Telangiectasia), M (Malignancy), A (Adult carrier breast risk), S (Sensitive to radiation), K (Klumsy)

Wilms tumor

• WT1, CTNNB1, AMER1, REST

• Sporadic / AD

• Pediatric kidney tumor (nephroblastoma), palpable abdominal mass, hematuria, hypertension.

WT - W (Wilms kidney tumor), T (Triggers screening with renal ultrasound)

Common AJ mutations

The BRCA1 Variants

• 185delAG (also written as c.68_69delAG)

• 5382insC (also written as c.5266dupC)

The BRCA2 Variant

• 6174delT (also written as c.5946delT)

APC c.3920T>A (p.Ile1307Lys), commonly known as I1307K