Papillary Thyroid Carcinoma

DNA copy number changes are uncommon in papillary thyroid carcinomas as compared with other poorly differentiated and well-differentiated thyroid carcinomas. Papillary thyroid carcinomas in CGH studies have variable rates of genetic aberrations and specific sites of aberrations. Nonetheless, several common aberrations have been identified, including gains on chromosomes lq, 5q, 6q 9q 13q, 19q, 21q, 4 and 7, and losses on chromosomes lp, 9q, 16q, 17, 19, and 22.9"11 Hemmer and associates10 found genetic aberrations in only 3 (12%) of 26 papillary thyroid carcinomas and reported a positive correlation between the presence of aberrations and older age (>70 years) and cervical lymph node metastasis. Singh and colleagues11 identified genetic aberrations in 10 (48%) of 21 papillary thyroid carcinoma cases. They reported that the loss of chromosome 22 was found only in younger patients (<45 years) and was associated

Gains

Losses

FIGURE 36-5. Comparative genomic hybridization image. The high intensity of green and red images demonstrates gains and losses on chromosomes, respectively.
TABLE 36-1. Comparison of Chromosomal Aberrations In Six Well-Differentiated and Seven Poorly Differentiated Papillary Thyroid Carcinomas

No.

Gender

Age

TNM

Type

Regions of Chromosomal Aberrations

1

F

74

in

Well

None

2

F

28

I

Well

17q25.3, 19ql3.33-43, 20pl3. 21q22.3, 22ql3.3

3

F

33

I

WeU

None

4

F

29

I

WeH

None

5

F

32

i

WeU

None

6

F

33

i

Well

None

7

F

81

in

Poorly

lql2-44

8

F

31

I

Poorly

2ql2.3-37, 15qll.2-26, 19p, 19q, 22qll-13.1, Xp,q

9

M

51

m

Poorly

None

10

F

27

n

Poorly

None

11

M

55

ni

Poorly

None

12

F

19

i

Poorly

None

13

F

35

IV

Poorly

1P13.2-36, lq23.3-32.1, 6q23.2-25.3, 13ql2.1-33.1,

16pl3.2-3, 18q21.1-3

with a higher rate of regional lymph node metastasis. In our study, no chromosomal aberration was found in 6 well-differentiated papillary thyroid carcinomas, but 3 (43%) of 7 poorly differentiated papillary thyroid carcinomas had chromosomal aberration. The most common chromosomal site was a gain on lq in 2 (29%) of the 7 poorly differentiated papillary thyroid carcinomas (Table 36-1). This region of lq abnormalities harbors a gene that encodes one of the receptors for the nerve growth factor (NTRK1), which is activated in about 15% of papillary thyroid carcinomas.12

Clonal chromosomal aberrations have been identified in almost half of the cytogenetically examined papillary thyroid carcinomas by other methods than CGH. The most frequent alteration has been an intrachromosomal rearrangement, a paracentric inversion in lOq (RET/PTC). This site is frequently the only change, and it is not detectable by

CGH 10,13-21

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