Cyclin D1 amplification in chromosomal band 11q13 is associated with overrepresentation of 3q21-q29 in head and neck carcinomas.
Eight cytogenetically characterized head and neck squamous cell carcinomas (HNSCCs) with CCND1 amplification in the form of a homogeneously staining region (hsr) in 11q13 were studied by COBRA FISH and FISH with specific probes to identify and characterize chromosomal segments added to the derivative chromosomes 11. In 4 of the tumors, it could be recognized that the material added was derived from the long arm of chromosome 3. The rearrangements were interpreted as der(11)hsr(11)(q13)t(3;11)(q21;q13) in 3 cases and as der(11)hsr(11)(q13)t(3;11)(q14;q13) in 1 case. In the other 4 cases, material from chromosomes 1, 16, or 19 was added to the derivative chromosomes 11. By further FISH analysis with 14 YAC clones spanning 3q13-q21 in the 4 tumors with der(11)hsr(11)t(3;11), it could be shown that they had different breakpoints at the molecular level, excluding the possibility that a particular gene was rearranged by the translocations. More surprisingly, gain of the 3q21-q29 segment was found in all 8 tumors with hsr in 11q13 and loss of 3p was seen in 7 of the tumors. These findings strongly indicate a synergistic effect of CCND1 amplification, loss of distal 11q, 3q gain and 3p deletion in HNSCC development and also suggests a mechanistic link between intrachromosomal amplification at 11q13 and recombination with distal 3q.
Jin
Yuesheng
Y
Department of Clinical Genetics, University Hospital, Lund, Sweden.
Jin
Charlotte
C
Wennerberg
Johan
J
Höglund
Mattias
M
Mertens
Fredrik
F
D000368:Aged; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D019938:Cyclin D1