Genetics

Question 1

AML translocations

Answer 1

t(8;21) RUNX1-RUNX1T1
inv(16) or t(16;16) CBFB-MYH11
t(15;17) PML-RARA
t(9;11) MLLT3-KMT2A
t(6:9) DEK-NUP214
inv(3) or t(3;3) GATA2
t(1;22) RBM15-MKL1
t(9;22)
NPM1
CEBPA

Question 2

T21 AML mutation

Answer 2

GATA1

Question 3

MDS mutations

Answer 3

Monosomy 7
Monosomy 5
-5q deletion
-7q deletion

Question 4

AML favorable mutations

Answer 4

CEBP alpha
NPM1
GATA1
t(8;21)
inv(16) or t(16;16)
t(15;17)
t(1;11)

Question 5

AML unfavorable genetics

Answer 5

FLT3-ITD
c-KIT
MDS
t(6;11), t(10;11)

Question 6

ALL translocations

Answer 6

t(12;21) ETV6-RUNX1
t(1;19) TCF3-PBX1
t(17;19) TCF3-HLF (DIC)
11q23 MLL - t(4;11) most common
t(9;22) BCR-ABL
t(5;14) IL3-IGH (hypereosinophilia)
hylerdiploidy/hypodiploidy
Trisomy 4, 10, 17

CRLF2 gene overexpression (Ph like)

t(8;14), t(2;8), t(8;22) - Burkitt Leukemia

Question 7

ALL favorable genetics

Answer 7

Hyperdiploid (>50)
Trisomy 4, 10, 17
t(12;21) ETv6-RUNX1

Question 8

ALL unfavorable genetics

Answer 8

hypodiploid (< 44)
MLL (KMT2A)
t(9;22)
iAMP21
t(17;19)

Question 9

T21 ALL

Answer 9

absence of favorable genetics

1/3 have JAK2 and unique fusion between P2RY8 and CRLF2 leading to CRLF2 overexpression

Question 10

Burkitt lymphoma translocations

Answer 10

t(8;14)
t(2;8)
t(8;22)

C-MYC
IGH
IGK
IGL

Question 11

Primary mediastinal B cell genetics

Answer 11

9p and 2p gains

JAK2
C-rel
SOCS1

Question 12

Lymphoblastic lymphoma genetics

Answer 12

Deletion TAL1
t(1;14)
t(11;14)
LOH at 6q

TAL1
TCRAO
RHOMB1
HOX11
NOTCH1

Question 13

ALCL translocations

Answer 13

t(2;5)

ALK
NPM

Question 14

Diffuse Large B Cell lymphoma genetics

Answer 14

2/3 express BCL-6
1/3 express cMYC

Activated B cell like t(14;18)

IRF4 translocations (favorable)

Question 15

Hodgkin lymphoma genetics

Answer 15

NFkB

9p24.1 alterations lead to increased PDL1

Question 16

Familial neuroblastoma genetics

Answer 16

ALK
PHOX2B (Hirschprung’s, central hypoventilation)
Deletion 1p36 or 11q14-23

Question 17

Sporadic NBL gremline mutations

Answer 17

NF-1
WT2
TP53
PTPN11

Question 18

Neuroblastoma genetics changes (non-hereditary)

Answer 18

Myc-N amplification
17q gain
1p36 (MYCNA)
11q23 
14q32
Whole chromosome gains
ALK
ATRX
ARID1a/1b
Ras pathway

Question 19

Syndromic Wilms genetics

Answer 19

11p13 WT1 - WAGR
11p13 WT1 - Denys-Drash
11p13 WT1 - Frasier
11p15 WT2 - BWS/isolated hemihypertrophy
2q37 DIS3L2 - Perlman
15q15 BUB1B - mosaic variegated aneuploidy
13q12 BRCA2 - fanconi anemia
Xp26 GPC3 - Simpson-Golabi-Behmel
P53

Question 20

Wilms genetic alterations

Answer 20

WT1 deletion/mutation
11p15 paternal uniparental disomy
WTX
CTNNB1 - WT1 associated (exon 3 deletion) or WTX associated (exon 7 and 8 deletions)
P53
LOH 1p and 16q
1q gain
DICER1 loss of function
DROSHA loss of function
SIX1/2 mutations
PTCH
MYC-N

Question 21

Congenital mesoblastic nephroma translocations

Answer 21

t(12;15) - cellular CMN

Question 22

Rhabdoid tumor

Answer 22

SMARCB1 (lack of INI1)

SMARCA4

Question 23

Rental cell carcinoma genetics

Answer 23

TFE3 gene on X chromosome

VHL- 3p26 deletion (tumor suppression)
Familial RCC - chromosome 3 translocation, succinate dehydrogenase (SDHB, SDHC, SDHD) mutation with pheochromocytoma

Question 24

Embryonal RMS genetics

Answer 24

LOH at 11p15

Question 25

Alveolar RMS genetics

Answer 25

FOXO1-PAX3 t(2;13) | FOXO1-PAX7 t(1;13)

Question 26

Synovial sarcoma translocation

Answer 26

t(X;18) SSX1-SYT

Question 27

Dermatofibrosarcoma protuberans translocation

Answer 27

t(17;22) COL1A1-PDGFB

Question 28

Malignant fibrous histiocytoma

Answer 28

19p+

Question 29

Angiomatoid fibrous histiocytoma

Answer 29

t(2;22) t(12;16) t(12;22) EWSR1-CREB1 TLS-ATF1 EWSR1-ATF1

Question 30

MPNST translocation

Answer 30

17q, 22q loss or rearrangement

Question 31

Fibrosarcoma translocations

Answer 31

t(X;18) t(2;5) t(7;22)

Question 32

Infantile fibrosarcoma translocations

Answer 32

t(12;15) ETV6-NTRK3

Question 33

Leiomyosarcoma translocations

Answer 33

Deletion 1p t(12;14) HMGA2 rearrangement

Question 34

Alveolar soft part sarcoma translocation

Answer 34

t(X;17) ASPSCR1-TFE3

Question 35

Hemangiopericytoma infantile form translocation

Answer 35

t(12;19) | t(13;22)

Question 36

Liposarcoma (myxoid) translocation

Answer 36

t(12;16) FUS-DDIT3

Question 37

Clear cell sarcoma translocation

Answer 37

t(12;22) EWSR1-ATF1

Question 38

Desmoplastic small round blue cell tumor translocation

Answer 38

t(11;22) EWS/WT1

Question 39

Ewing sarcoma translocations

Answer 39

t(11;22) - most common, EWS-FLI1 t(21;22) EWS-ERG Chromosomal changes in 1 and 16 Trisomy 8 and 12

Question 40

Osteosarcoma common genetic alterations

Answer 40

P53 (17p13) RB1 (13q14) Bloom syndrome RecQL3 (15q26.1) Rothmund-Thomson RecQL4 (8q24.3)

Question 41

Retinoblastoma genetics

Answer 41

RB1 (13q14) tumor suppressor P53 (MDM2, MDM4 amplification) BCOR mutations SYK upregulation

Question 42

Testicular GCT cytogenetics

Answer 42

Prepubertal: 6p and 1q deletions Adolescents: i(12p), loss of 13, +21 Extragonadal: +X

Question 43

Brain tumor predisposition syndromes and their mutation

Answer 43

``` NF1: 17q11.2 Neurofibromin NF2: 22q12.2 Merlin TS: 9q34, 16p13.3 hamartin and Tuberin Li-Fraumeni: 17p13.1 TP53 VHL: 3p25.3 VHL Turcot: 5q21-22, 3p21 APC Gordon: 9q22 PTCH1 ```

Question 44

LGG genetics

Answer 44

BRAF-K1AA1549 fusion BRAF V600E mutations FGFR1, PTPN11, NTRK2 fusion

Question 45

DIPG genetics

Answer 45

H3K27M

Question 46

ATRT mutation

Answer 46

SMARCB1 (INI1 negative) | SMARCA4

Question 47

Cancers associated with BWS

Answer 47

``` Wilms Hepatoblastoma Neuroblastoma rhabdomyosarcoma Adrenocorical carcinoma ```