8-9. EYE AND SKIN
Total number of publications: 30
Total number of cases: 784
Total number of amplifications: 152
Eye tumors: 86 amplifications out of 580 cases
Tumor
8.1
Loss
Eye melanoma
Amplicon
1p
3
6p
6p21-pter
6q*
8p
8q
8q24-qter
8.1
8.1
9p21-pter
11q23-qter*
16q12-qter
22q11-q12
UVEAL MELANOMA (0/333 cases)
Percentage
(number of
cases)
19 (4/21)
57 (12/21)
40 (4/10)
55 (6/11)
33 (7/21)
19 (4/21)
100 (10/10)
64 (7/11)
27 (3/11)
24 (5/21)
19 (4/21)
40 (4/10)
Amplified
genes
(studied from
the same
cases)
Reference
1,2
1,2
1
2
1,2
1,2
1
2
2
1,2
1,2
1
Tschentscher F, Prescher G, Horsman DE, White VA, Rieder H, Anastassiou G, Schilling H, Bornfeld N,
Bartz-Schmidt KU, Horsthemke B, Lohmann DR, Zeschnigk M: Partial deletions of the long and short arm of
chromosome 3 point to two tumor suppressor genes in uveal melanoma. Cancer Res 2001, 61:3439-3442.
UVEAL MELANOMA (?/31 cases)
Comment: Number of cases was not clearly defined, but high-level amplifications were present at 1q, 8p11.2,
8q11.2qter, 8q, 20q11.2qter, 20q13.1qter, 22q13, and 22.
Aalto Y, Eriksson L, Seregard S, Larsson O, Knuutila S: Concomitant loss of chromosome 3 and whole arm
losses and gains of chromosome 1, 6, or 8 in metastasizing primary uveal melanoma. Invest Ophthalmol Vis
Sci 2001, 42:313-317.
8.1
8.1
UVEAL MELANOMA (1/5 cases)
amp(8q13qter)
Naus NC, van Drunen E, de Klein A, Luyten GPM, Paridaens DA, Alers JC, Ksander BR, Beverloo HB, Slater
RM: Characterization of complex chromosomal abnormalities in uveal melanoma by fluorescence in situ
hybridization, spectral karyotyping, and comparative genomic hybridization. Genes Chromosomes Cancer
2001, 30:267-273.
UVEAL MELANOMA
ADDITIONAL LITERATURE
Tschentscher F, Prescher G, Zeschnigk M, Horsthemke B, Lohmann DR: Identification of chromosomes 3, 6,
and 8 aberrations in uveal melanoma by microsatellite analysis in comparison to comparative genomic
hybridization. Cancer Genet Cytogenet 2000, 122:13-17.
8.1
Eye melanoma: 36 amplifications out of 390 cases
8.2
8.2
8.2
8.2
Spitz nevi, benign
melanocytic neoplasm
SPITZ NEVI (3/22 cases)
amp(11p)/amp (11p) /amp (11p)
11p
18 (3/17)
3
Harvell JD, Bastian BC, LeBoit PE: Persistent (recurrent) Spitz nevi: a histopathologic, immunohistochemical,
and molecular pathologic study of 22 cases. Am J Surg Pathol 2002, 26:654-661.
MELANOMA, SPITZOID MALIGNANT (0/1 case)
Mihic-Probst D, Zhao J, Saremaslani P, Baer A, Komminoth P, Heitz PU: Spitzoid malignant melanoma with
lymph-node metastasis. Is a copy-number loss on chromosome 6q a marker of malignancy? Virchows Arch
2001, 439:823-826.
CONGENITAL MELANOCYTIC NEVI (?/29 cases)
Comment: Amplifications were not determined.
Bastian BC, Xiong J, Frieden IJ, Williams ML, Chou P, Busam K, Pinkel D, LeBoit PE: Genetic changes in
neoplasms arising in congenital melanocytic nevi differences between nodular proliferations and melanomas.
Am J Pathol 2002, 161:1163-1169.
8.2
Spitz nevi: 6 amplifications out of 69 cases
8.3
8.3
8.3
8.3
RETINOBLASTOMA (4/20 cases)
amp(1q21)/amp(1q21,2p23p24)/amp(2p11.2p13,2p15p21,2p23p25)/amp(2p23p24)
Mairal A, Pinglier E, Gilbert E, Peter M, Validire P, Desjardins L, Doz F, Aurias A, Couturier J: Detection of
chromosome imbalances in retinoblastoma by parallel karyotype and CGH analyses. Genes Chromosomes
Cancer 2000, 28:370-379.
RETINOBLASTOMA (?/50 cases)
Comment: Amplifications were not determined.
Chen D, Gallie BL, Squire JA: Minimal regions of chromosomal imbalance in retinoblastoma detected by
comparative genomic hybridization. Cancer Genet Cytogenet 2001, 129:57-63.
RETINOBLASTOMA (9/26 cases)
amp(6p)/amp(6p)/amp(6p)/amp(1q,2p13p25,6p,Xq26q28)/amp(Xp11.2p22.3,Xq12q13)/amp(1q32,6p)/amp(6p
)/amp(6p)/amp(6p)
Comment:
1/13 young (2.0-9.8 mo) or (median 6 mo) children age at operation:
amp(6p)
8/13 older (36.4-84.1 mo) or (median 50 mo) children age at operation:
amp(6p)/amp(6p)/amp(1q,2p13p25,6p,Xq26q28)/amp(Xp11.2p22.3,Xq12q13)/amp(1q32,6p)/amp(6p)/amp(6p
)/amp(6p)
Herzog S, Lohmann DR, Buiting K, Schüler A, Horsthemke B, Rehder H, Rieder H: Marked differences in
unilateral isolated retinoblastomas from young and older children studied by comparative genomic
hybridization. Hum Genet 2001, 108:98-104.
RETINOBLASTOMA (16/25 cases)
amp(6p)/amp(6p)/amp(1p11q32,6p)/amp(6,20)/amp(6p)/amp(1q11q24,6p)/amp(1q,6p)/amp(6p)/amp(Xp22)/
amp(6p)/amp(2q12pter)/amp(1q,2p12pter)/amp(2p)/amp(2p21p25)/amp(2p12pter)/amp(2p22p24)
Lillington DM, Goff LK, Kingston JE, Onadim Z, Price E, Domizio P, Young BD: High level amplification of
N-MYC is not associated with adverse histology or outcome in primary retinoblastoma tumours. Br J Cancer.
2002, 87:779-782.
8.3
Retinoblastoma: 44 amplifications out of 121 cases
8.4
ADENOCARCINOMA OF THE CILIARY EPITHELIUM, PLEOMORPHIC (0/1 case)
Nicolo M, Nicolo G, Zingirian M: Pleomorphic adenocarcinoma of the ciliary epithelium: a clinicopathological,
immunohistochemical, ultrastructural, DNA-ploidy and comparative genomic hybridization analysis of an
unusual case. Eur J Ophthalmol 2002, 12:319-323.
Skin tumors: 66 amplifications out of 204 cases
9.1
Skin melanoma
None
1p21-p22
3q
4q12
5p14.3-pter
5q15-q34
6q21
7q32-q34
7q33-qter
8p21-pter
8q12-q13
9p22-pter
10q21-qter
11q13.3-q14.2
17q25
9.1
13 (4/32)
13 (4/32)
3 (1/32)
3 (1/32)
13 (4/32)
28 (9/32)
33 (1/3)
3 (1/32)
25 (8/32)
3 (1/32)
78 (25/32)
59 (19/32)
3 (1/32)
3 (1/32)
4
5
5
5
5
5
5
4
5
5
5
5
5
5
5
ACRAL MELANOMA (17/30 cases)
amp(7p21pter,12q14q21)/amp(3q11q13.3,11q14q22)/amp(5p,5q11.2,11p15,16q22qter)/amp(1p31pter,12q14
q21)/amp(11q13)/amp(11q13,22q11)/amp(7p15pter,22q11q12)/amp(11q13,22q11q13.1)/amp(11q13,22q11q1
3.1)/amp(11q12q13,20q)/amp(11q13,16q21q22)/amp(5p12p13,22q13)/amp(22q13)/amp(5p22pter,6p23pter)/
amp(1p13,1q32qter,21q21q22)/amp(6p12p21,6p22p24)/amp(11q13)
Comment:
15/15 acral melanomas:
amp(7p21pter,12q14q21)/amp(3q11q13.3,11q14q22)/amp(5p,5q11.2,11p15,16q22qter)/amp(1p31pter,12q14
q21)/amp(11q13)/amp(11q13,22q11)/amp(7p15pter,22q11q12)/amp(11q13,22q11q13.1)/amp(11q13,22q11q1
3.1)/amp(11q12q13,20q)/amp(11q13,16q21q22)/amp(5p12p13,22q13)/amp(22q13)/amp(5p22pter,6p23pter)/
amp(1p13,1q32qter,21q21q22)
2/15 superficial spreading melanomas:
amp(6p12p21,6p22p24)/amp(11q13)
Bastian BC, Kashani-Sabet M, Hamm H, Godfrey T, Moore DH 2nd, Brocker E-B, LeBoit PE, Pinkel D: Gene
amplifications characterize acral melanoma and permit the detection of occult tumor cells in the surrounding
skin. Cancer Res 2000, 60:1968-1973.
9.1
9.1
9.1
9.1
MELANOMA, NODULAR MALIGNANT (1/1 cases)
amp(6p,8q22qter)
Greulich KM, Utikal J, Peter R-U, Krahn G: c-MYC and nodular malignant melanoma. Cancer 2000, 89:97103.
METASTATIC MELANOMA, CUTANEOUS (?/1 case)
Comment: Amplifications were not determined.
Wiltshire RN, Dennis TR, Sondak VK, Meltzer PS, Trent JM: Application of molecular cytogenetic techniques
in a case study of human cutaneous matastatic melanoma. Cancer Genet Cytogenet 2001, 131:97-103.
MELANOMA (10/24 cases)
amp(1p13)/amp(1p12p21,1p22p31)/amp(4q12q13.3,8q23qter)/amp(7p11.2pter,8q22qter)/amp(7q11.2qter)/a
mp(7q11.2qter)/amp(7q21.3qter)/amp(1p12p13,1q,Xq21.1qter)/amp(1p12p21,1p22p31)/amp(20q13.1qter)
Comment:
7/16 primary melanomas:
amp(1p13)/amp(1p12p21,1p22p31)/amp(4q12q13.3,8q23qter)/amp(7p11.2pter,8q22qter)/amp(7q11.2qter)/a
mp(7q11.2qter)/amp(7q21.3qter)
3/8 metastatic melanomas:
amp(1p12p13,1q,Xq21.1qter)/amp(1p12p21,1p22p31)/amp(20q13.1qter)
Balázs M, Ádám Z, Treszl A, Bégány Á, Hunyadi J, Ádány R: Chromosomal imbalances in primary and
metastatic melanomas revealed by comparative genomic hybridization. Cytometry 2001, 46:222-232.
MELANOMA
ADDITIONAL LITERATURE
Llewellyn K, Barnhill RL: Distinguishing Spitz tumors from malignant melanoma: potential role of comparative
genomic hybridization and fluorescence in situ hybridization in diagnosis and prognosis. Adv Anat Pathol
2001, 8:249-254.
9.1
Skin melanoma: 60 amplifications out of 91 cases
9.2
9.2
9.2
SKIN CARCINOMA (1/1 case)
amp(17q24q25)
Popp S, Waltering S, Holtgreve-Grez H, Jauch A, Proby C, Leigh IM, Boukamp P: Genetic characterization of
a human skin carcinoma progression model: from primary tumor to metastasis. J Invest Dermatol 2000,
115:1095-1103.
SQUAMOUS CELL SKIN CARCINOMA (1/1 case)
amp(7p12p13)
Shimizu T, Izumi H, Oga A, Furumoto H, Murakami T, Ofuji R, Muto M, Sasaki K: Epidermal growth factor
receptor overexpression and genetic aberrations in metastatic squamous-cell carcinoma of the skin.
Dermatology 2001, 202:203-206.
SQUAMOUS CELL SKIN CARCINOMA (?/21 cases)
Comment: Amplifications were not determined.
Popp S, Waltering S, Herbst C, Moll I, Boukamp P: UV-B-type mutations and chromosomal imbalances
indicate common pathways for the development of Merkel and skin squamous cell carcinomas. Int J Cancer
2002, 99:352-360.
9.3
Merkel cell carcinoma
3p*
5q*
8p*
10*
11q23-qter
13q11-q22
17p
Additional reference
46 (11/24)
21 (5/24)
21 (5/24)
33 (8/24)
21 (5/24)
33 (8/24)
25 (6/24)
6
6
6
6
6
6
6
7
9.3
9.3
MERKEL CELL CARCINOMA (?/31 cases)
Comment: Amplifications were not determined.
Van Gele M, Leonard JH, Van Roy N, Van Limbergen H, Van Belle S, Cocquyt V, Salwen H, De Paepe A,
Speleman F: Combined karyotyping, CGH and M-FISH analysis allows detailed characterization of
unidentified chromosomal rearrangements in Merkel cell carcinoma. Int J Cancer 2002, 101:137-145.
MERKEL CELL CARCINOMA (4/19 cases)
amp(4p)/amp(6p)/amp(1q22q24)/amp(5p)
Larramendy ML, Koljonen V, Bohling T, Tukiainen E, Knuutila S: Recurrent DNA copy number changes
revealed by comparative genomic hybridization in primary Merkel cell carcinomas. Mod Pathol 2004, 17:561567.
9.3
Merkel cell carcinoma: 4 amplifications out of 74 cases
9.4
BASAL CELL CARCINOMA (?/15 cases)
Comment: Amplifications were not determined.
Ashton KJ, Weinstein SR, Maguire DJ, Griffiths LR: Molecular cytogenetic analysis of basal cell carcinoma
DNA using comparative genomic hybridization. J Invest Dermatol 2001, 117:683-686.
Concerning Losses: 10% of the cases must be aberrant and the number of aberrant cases at least three; findings in
parentheses are examples of highly frequent aberrations that fail to meet the 3 cases/10% criteria; Boldface indicates that
more than 30% of the cases detected in a study of at least 10 cases were aberrant;
*Description of a region, e.g. 6q21-q22, implies that in a variety of cases the loss was located within the area but it did not
necessarily affect the whole area in all cases. The described regions may therefore not be considered analogous with
minimal overlapping area. Furthermore, in some single cases the loss area may extend beyond the region described. As a
whole, the description should be considered a flexible way to summarize critical areas of recurrent DNA copy number
changes in that particular tumor type. Description without an asterisk indicates minimal overlapping areas.
Concerning Amplicons: Boldface indicates recurrent established amplicons (at least three cases and frequency more than
5%).
REFERENCES
1.
Gordon KB, Thompson CT, Char DH, O'Brien JM, Kroll S, Ghazvini S, Gray JW: Comparative genomic hybridization in
the detection of DNA copy number abnormalities in uveal melanoma. Cancer Res 1994, 54:4764-4768.
2.
Speicher MR, Prescher G, du Manoir S, Jauch A, Horsthemke B, Bornfeld N, Becher R, Cremer T: Chromosomal gains
and losses in uveal melanomas detected by comparative genomic hybridization. Cancer Res 1994, 54:3817-3823.
3.
Bastian BC, Wesselmann U, Pinkel D, LeBoit PE: Molecular cytogenetic analysis of Spitz nevi shows clear differences
to melanoma. J Invest Dermatol 1999, 113:1065-1069.
4.
Wiltshire RN, Duray P, Bittner ML, Visakorpi T, Meltzer PS, Tuthill RJ, Liotta LA, Trent JM: Direct visualization of the
clonal progression of primary cutaneous melanoma: application of tissue microdissection and comparative genomic
hybridization. Cancer Res 1995, 55:3954-3957.
5.
Bastian BC, LeBoit PE, Hamm H, Brocker EB, Pinkel D: Chromosomal gains and losses in primary cutaneous
melanomas detected by comparative genomic hybridization. Cancer Res 1998, 58:2170-2175.
6.
Van Gele M, Speleman F, Vandesompele J, Van Roy N, Leonard JH: Characteristic pattern of chromosomal gains and
losses in Merkel cell carcinoma detected by comparative genomic hybridization. Cancer Res 1998, 58:1503-1508.
7.
Harle M, Arens N, Moll I, Back W, Schulz T, Scherthan H: Comparative genomic hybridization (CGH) discloses
chromosomal and subchromosomal copy number changes in Merkel cell carcinomas. J Cutan Pathol 1996, 23:391-397.