Required Readings Flashcards Preview

Rotation - Molecular > Required Readings > Flashcards

Flashcards in Required Readings Deck (45)
Loading flashcards...
1

What are the two functional classes of balanced chromosomal rearrangements in cancer?

Aberrations that result in the formation of a chimeric fusion gene with new or altered activity

Aberrations that result in deregulated expression of a structurally normal gene

2

What types of tumors have the strongest association with chromosomal rearrangement?

Hematologic cancers

Tumors of mesenchymal origin

3

What are the two major classes of genes which form chimeric fusion products?

Tyrosine kinase genes (eg ABL1)

Transcription factor genes (eg FLI1)

 

4

Besides CML, what tumors express ABL fusions sensitive to small molecule RTK inhibitors?

T-cell ALL

(ABL1-NUP214)

5

What are the two classic translocations seen in Ewing sarcoma?

t(11;22)(q24.1-q24.3;q12.2)
EWSR1-FLI1

t(21;22)(q22.3;q12.2)
EWSR1-ERG

(both FLI1 and ERG are part of the ETS family of transcription factors)

6

Describe the classic genetic change and gene fusion product:

NSCLC

 

inv(2)(p22-p21p23)

EML4-ALK

7

Describe the classic genetic change and gene fusion product:

Anaplastic large cell lymphoma

t(2;5)(p23;q35)

ALK-NPM1

8

Describe the classic genetic change and gene fusion product:

Multiple myeloma

Several with IgH...

t(4;14) - WHSC1
t(6;14) - Cyclin D1
t(11;14) - Cyclin D3
t(14;16) - MAF
t(14;20) - MAF

9

Describe the classic genetic change and gene fusion product:

CML

t(9;22)(q34.1;q11.23)

BCR-ABL1

10

Describe the classic genetic change and gene fusion product:

Myeloid neoplasms associated with eosinophilia
(two!)

del(4)(q12q12)
FIP1L1-PDGFRA

t(5;12)(q31-q32;p13)
PDGFRB-ETV6

11

Describe the classic genetic change and gene fusion product:

Papillary thyroid cancer
(Two!)

inv(10)(q11.2q11.2)
RET-NCOA4

inv(10)(q11.2q21)
RET-CCDC6

12

Describe the classic genetic change and gene fusion product:

Acute megakaryoblastic leukemia

t(1;22)(p13;q13)

RBM15-MKL1

13

Describe the classic genetic change and gene fusion product:

Follicular thyroid carcinoma

t(2;3)(q12-q14;p25)

PAX8-PPARG

14

Describe the classic genetic change and gene fusion product:

Prostatic adenocarcinoma

del(21)(q22.3q22.3)

TMPRSS2-ERG

15

Describe the key chromosomal imbalance and the gene it involves for:

Breast cancer

amp(1)(q32.1)

IKBKE

16

Describe the key chromosomal imbalance and the gene it involves for:

Neuroblastoma

amp(2)(p24.1)

MYCN

17

Describe the key chromosomal imbalance and the gene it involves for:

Malignant melanoma

amp(3)(p14.2-p14.1)

MITF

18

Describe the key chromosomal imbalance and the gene it involves for:

Polycythemia vera

+9p

JAK2

19

Describe the key chromosomal imbalance and the gene it involves for:

NSCLC

amp(14)(q13)

NKX2-1

20

Describe the key chromosomal imbalance and the gene it involves for:

Renal cell carcinoma

del(3p26-p25)

VHL

21

Describe the key chromosomal imbalance and the gene it involves for:

Colon cancer
(Two!)

del(5)(q21-q22)
APC

del(4)(q12)
REST

22

Describe the key chromosomal imbalance and the gene it involves for:

Retinoblastoma

del(13)(q14.2)

RB1

23

Describe the key chromosomal imbalance and the gene it involves for:

Wilm's tumor

del(X)(q11.1)

FAM123B

24

What are some translocation partners for c-MYC in Burkitt's lymphoma?

14q, 22q, 2p

25

What aberrations can occur as initiating events?

Which can occur as progression events?

Initiating: Translocations & mutations

Progression: Translocations, mutations, & amplifications

26

What are the six categories of oncogenes (by gene product?

Transcription factors

Chromatin remodelers

Growth factors

Growth factor receptors

Signal transducers

Regulators of apoptosis

27

What is the effect of EWS gene fusion?

When EWS is fused to a DNA-binding domain, it greatly stimulates gene transcription.

28

Describe the tumorigenic effect of TMPR fusion in prostate cancer.

TMPR522 has an androgen responsive promoter element; when fused with an ETS gene (ETV1, ERG1) it increases proliferation and inhibits apoptosis of prostatic glandular cells.

29

What are the two kinds of enzymes which remodel chromatin? How do they contribute to tumorigenesis?

1. ATP-dependent enzymes that move the positions of nucleosomes.

2. Enzymes that modify the N-terminal tails of histones.

*Both cause epigenetic modification that determines chromatin's transcriptional capacity

30

Describe MLL's contribution to tumorigenesis in AML and ALL.

MLL is a very large complex including components of transcription complexes and histone methylators. Its fusion with one of many proteins causes deregulation of homeobox genes (encoding transcription factors), EPHA7 (which encodes an RTK), and microRNAs.