Genitourinary cancer

Question 1

Tumors in patients with DNA repair gene mutations may be susceptible to. . .

Answer 1

PARP inhibition

The principle of PARP inhibition in these tumors is that they still rely on base excision repair to maintain a low enough mutation rate for survival (although it is still increased relative to baseline).

Question 2

Targeting MSI-H or dMMR tumors

Answer 2

PARP inhibitors

Platinum-based chemotherapy (cisplatin)

Immunotherapy (pembrolizumab, nivolumab)

Question 3

Subtypes of genitourinary tumors which benefit most from checkpoint inhibitor therapy

Answer 3

Luminal-infiltrated and basal/squamous

Question 4

The most common rearrangement in human solid tumors

Answer 4

TMPRSS2-ERG

Which occurs in approximately half of prostate carcinomas, making it the most common.

Question 5

Molecular progression of prostate carcinoma

Answer 5

1. TMPRSS2-ERG translocation
2. PTEN loss, TERT activation
3. AR amplification, TP53 mutation/deletion, RB1 deletion

Question 6

HOXB13 G84E

Answer 6

Germline variant which carries a 3-fold risk of developing prostate carcinoma

Question 7

Seven oncogenic drivers of prostate cancer

Answer 7

Gene fusions:
* ERG (46% of cases)
* ETV1 (8% of cases)
* ETV4 (4% of cases)
* FLI1 (1% of cases)

Mutations:
* SPOP (11% of cases)
* FOXA1 (3% of cases)
* IDH1 (1% of cases)

Question 8

Inherited predisposition to aggressive prostate cancer

Answer 8

Distribution of inherited DNA repair gene mutations in men with metastatic prostate cancer

Question 9

Luminal bladder cancers

Answer 9

Characterized by CK20, GATA3, and FOXA1 positivity.

Molecularly subdivided into three groups: luminal-papillary (35%), luminal infiltrated (19%), and luminal (6%)

Question 10

Basal/squamous bladder cancers

Answer 10

Characteruzed by CK5/6 and CK14 positivity, negativity for GATA3 and FOXA1.

Molecularly classified as basal/squamous (35%)

Question 11

Fifth molecular subgroup of bladder cancers

Answer 11

Neuronal

Question 12

Luminal-papillary bladder cancer subgroup - defining features

Answer 12

FGFR3 mutation/fusion/amplification

Papillary histology

Overall low risk, tend to respond to FGFR3 inhibitors.

Question 13

Luminal-infiltrated bladder cancer subgroup - defining features

Answer 13

TWIST, ZEB1 (EMT markers)
Moderate PD-L1, CTLA-4
Wild-type TP53
miR-200 family

Low response to cisplatin, tend to be treated with immunotherapy.

Question 14

miR-200 family

Answer 14

miR-200a, -200b, -200c, -141, -429

Emerging miRNA family that has been shown to play crucial roles in cancer initiation and metastasis. Found in two clusters on chromosomes 1 (200a/b/429) and 12 (200c/141).

Question 15

Luminal bladder cancer subgroup - defining features

Answer 15

CK20, SNX31, UPKs

Question 16

Basal/squamous bladder cancer subgroup - defining features

Answer 16

Female individual
Squamous morphology
Basal keratin markers
High PD-L1, CTLA4

Respond well to both platinum-based chemotherapy and checkpoint inhibitors

Question 17

Neuronal bladder cancer subgroup - defining features

Answer 17

SOX2
DLX6
MSI1
PLEKHG4B
E2F3/SOX4 amplification
Highly proliferative

Respond to etoposide/cysplatin chemotherapy

Question 18

Types of bladder cancer which benefit most from immunotherapy

Answer 18

Basal/squamous and luminal-infiltrated