Prep: Genetics

Essentials to Know:Solid Tumors

100

• Alveolar rhabdomyosarcoma (ARMS)

•t(1;13) 

• ARMS: PAX7 (1) and FOXO1 (13; aka. FKHR) translocation

200

 • Alveolar rhabdomyosarcoma 

•t(2;13)

 • ARMS: PAX3 (2) and FOXO1 (13; aka. FKHR) translocation

300

 • Ewing sarcoma

•t(11;22) 

• Ewing sarcoma: EWS (22) and FLI1 (11) 

• In Ewing sarcoma, EWS can have other fusion partners such as ERG (21), ETV1 (7), etc. 

• EWS-FLI1 is also found in other Ewing Sarcoma Family of tumors including peripheral PNET (ETV1 [7]) and DSRCT (WT1 [11] 

400

• Sporadic Wilms tumor 

• WAGR: Wilms tumor, aniridia, genitourinary malformations, developmental delay 

• Denys-Drash syndrome

•WT1 

500

• Rhabdoid tumors (including Atypical teratoid rhabdoid tumor ): 

• Schwannomatosis

• SMARCB1  

Essentials to Know:Hematology

100

• AML 

 • Core Binding Factor-related AML 

• Found most commonly in FAB M2 (AML with maturation)

•t(8;21) 

• AML M2: RUNX1 (21) and RUNX1T1 (8) translocation (aka. AML1-ETO) 

200

Accounts for 25% of all B-ALL and is associated with a good prognosis

t(12;21) 

B-ALL: ETV6 (12) and RUNX1 (21) translocation (aka. TEL-AML1)

300

 • Burkitt's lymphoma/leukemia.

 • Found in 80% of Burkitt's lymphoma . 

•t(8;14) 

• cMYC (8) and IGH (14) translocation 

• Other translocations with the κ light (2) or λ light chain promoter (22) also occur but are less common

400

•  Infantile ALL and AML commonly M4/M5: KMT2A.  • Numerous different fusion partners.

• 11q23 fusions 

500

 • Historically dismal outcomes in B-ALL. Intermediate outcomes with TKIs 

• Defining lesion of CML 

• Can also refer to the translocation of extraskeletal myxoid chondrosarcoma. 

t(9;22) 

• B-ALL and CML: BCR (22) and ABL1 (9) translocation

Mutations and Epigenetic Defects

100

• Down Syndrome-related acute megakaryocytic leukemia  (AMKL) and transient abnormal myelopoiesis (TAM)

•Found in almost all patients with mutation almost always in Exon 2 

• Arises in the fetal liver and is present in both AMKL and TAM 

• Second hit mutation required to progress from TAM to AMKL 

•GATA1 

200

• LCH: Found in 60% 

• Some pilocytic astrocytomas: Found in 15% 

• Pleomorphic Xanthoastrocytoma: Found in 60%

 • Melanoma: Found in 45% 

• Papillary thyroid carcinoma (other adult cancers)

•BRAFV600E 

300

• DIPG: Found in 80%

 • Same mutation also seen in other midline gliomas

•H3K27M mutation 

400

•Neuroblastoma: Found in 20%, most common amplification 

 •High-risk feature

•MYCN

500

 • Juvenile myelomonocytic leukemia : Found in 90% .

• Activating germline or somatic mutations in the RAS pathway .

• Possible spontaneous resolution with Noonan's syndrome .

NF1 

NRAS 

KRAS 

PTPN11 

CBL 1

More essentials to Know:Hematology

100

 • Core Binding Factor-related AML 

• Found most commonly AML with eosinophilia  

• inv(16) 

• AML M4eo: Inversion leads to fusion of CBFB (16) and MYH11 (16) 

200

 • Associated with AML M3 (APML)

• t(15;17) 

• AML M3: PML (15) and RARa (17) translocation 

300

• Paroxysmal nocturnal hemoglobinuria (PNH) .

•PIGA 

Immunologic disorders

100

 • HLH

•Familial HLH: Most common mutations affect the perforin pathway (PRF1, UNC13D, STX11, STXBP2) 

• Elevated risk of HLH: Griscelli syndrome (RAB27A), Hermansky-Pudlack syndrome (AP3B1), XLPS (SH2D1A or XIAP), XMEN syndrome (MAGT1)

PRF1 

UNC13D 

STX11 

RAB27A S

H2D1A 

XIAP

200

 • Autoimmune lymphoproliferative syndrome  

FAS 

FASL

 CASP10  

300

•Chronic granulomatosis disease

• gp47phox  : Found in 25%, autosomal recessive

 •gp91phox : Found in 70%, X-linked