CKS1B amplification is a frequent event in cutaneous squamous cell carcinoma with aggressive clinical behaviour.
Genetic mechanisms giving rise to the development of cutaneous squamous cell carcinoma (cSCC) are poorly understood and development of genomic high resolution techniques has led to a better knowledge of the genetic basis of several human cancers. In this study, 16 cSCC were analyzed using array comparative genomic hybridization (arrayCGH). The most common aberrations found were gains of 3q11q13, 1q21.3q25, 13q34, and 19p13, and losses of 1p36p31, 3p24p21, 10p15q22, and 13q11q21. We detected gains (3/16) and amplification (1/16) of the 1q21.1q21.3 region. A potential candidate gene in this region, CKS1B (1q21.2), was selected for validation in an independent cohort and correlations with clinicopathological features were carried out. CKS1B gene and protein status were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in a series of 53 cSCC, 22 actinic keratoses (AK), and 10 normal skin samples. cSCC presented a higher frequency of chromosome 1 polysomy than AK (70% vs. 46%, P = 0.047). Association between CKS1B protein overexpression and both polysomy and amplification was demonstrated in cSCC (P < 0.001). Regarding amplifications, 11 cSCC patients (21%) presented CKS1B gene amplification. Interestingly, 8/11 (73%) patients who showed a CKS1B amplification had presented metastatic spread (mcSCC). Differences between the presence of CKS1B amplification and the presence or absence of mcSCC were observed (mcSCC [8/14] vs. cSCC [3/39]) (P < 0.001). Several drugs targeting CKS1B have been reported and may be useful for treating patients with cSCC and CKS1B amplifications.
Salgado
Rocío
R
Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain.
Toll
Agustí
A
Alameda
Francesc
F
Baró
Teresa
T
Martín-Ezquerra
Gemma
G
Sanmartín
Onofre
O
Martorell-Calatayud
Antonio
A
Salido
Marta
M
Almenar
Sergio
S
Solé
Francesc
F
Pujol
Ramon M
RM
Espinet
Blanca
B
D000368:Aged; D000369:Aged, 80 and over; D042846:CDC2-CDC28 Kinases; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D002869:Chromosome Aberrations; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
C093090:CKS1B protein, human; D002352:Carrier Proteins; D042846:CDC2-CDC28 Kinases; D018844:Cyclin-Dependent Kinases