Evaluation of the clonal origin of multiple primary melanomas using molecular profiling.
Numerous investigations have been conducted using molecular profiling to evaluate the possible clonal origin of second malignancies in various cancer types. However, to date no study assessing clonality of multiple primaries has been conducted in melanoma. In this investigation using patients treated at a specialist melanoma treatment center, we compared the somatic mutational profiles of pairs of melanomas designated as independent on the basis of thorough assessment of their clinical and pathologic characteristics. We used a set of highly polymorphic genetic markers selected on the basis of their chromosomal positions and the frequencies of reported allelic losses at these genetic loci. Our statistical testing strategy showed no significant evidence of clonal origin of the two primaries in 17 of the 19 patients examined. The results suggest that most second melanomas designated as independent primary tumors on the basis of their clinicopathologic features are indeed independent occurrences of the disease, supporting the validity of the criteria used by experienced pathologists in distinguishing new primaries from metastases.
Orlow
Irene
I
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Tommasi
Diana V
DV
Bloom
Bradley
B
Ostrovnaya
Irina
I
Cotignola
Javier
J
Mujumdar
Urvi
U
Busam
Klaus J
KJ
Jungbluth
Achim A
AA
Scolyer
Richard A
RA
Thompson
John F
JF
Armstrong
Bruce K
BK
Berwick
Marianne
M
Thomas
Nancy E
NE
Begg
Colin B
CB
D006801:Humans; D019656:Loss of Heterozygosity; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology