title: Genomic aberrations in squamous cell lung carcinoma related to lymph node or distant metastasis.
abstract: About 50% of patients presenting with resectable lung cancer develop distant metastases within 5 years. Genomic markers predicting metastatic behaviour of squamous cell lung carcinoma (SCC) are currently underexposed. We analyzed a cohort of patients with primary SCC using array-based comparative genomic hybridization (aCGH) to identify which genomic aberrations are related to metastatic behaviour. The cohort consisted of 34 patients with a follow-up of at least 5 years, 8 with metastases in regional lymph nodes only and 26 patients without any metastases at the time of surgery. Eleven of the latter 26 developed metastases in distant organs within 3 years after surgery. Copy number changes observed in at least 40% of all SCC included gains at chromosomal arms 3q, 5p, 8q, 19q, 20p, 22q and losses at 3p, 4p, 4q, 5q, 8p and 9p. High copy number amplifications were observed at 2p15-p16, 3q24-q29, 8p11-p12, 8q23-q24, and 12p12, containing candidate oncogenes such as BCL11A, REL, ECT2, PIK3CA, ADAM9, MYC and KRAS. Amplification of 2p15-p16 is a novel finding in SCC. Another novel finding is the homozygous deletion observed at 4q33-34.1 in 15% of the SCC cases. Gains at 7q36, 8p12, 10q22, 12p12, loss at 4p14 and the homozygous deletions at 4q occurred significantly more frequent in SCC from patients with lymph node metastases only. SCC from patients with distant metastases showed a significantly higher gain frequency at 8q22-q24 and loss at 8p23 and 13q21, and a significantly lower gain frequency at 2p12 and 2p16 and loss at 11q25 compared with SCC from patients without metastases. Of these, gains at 7q, 8p and 10q were restricted to SCC with lymph node metastasis and gain at 8q was restricted to patients with distant metastasis. Two genomic aberrations, i.e. loss of 4p and gain of 19q12 were observed more frequently in SCC with only lymph node metastases as compared to SCC with distant metastases. In conclusion, we identified genomic aberrations in primary SCC that were related to lymph node or distant metastases.
authors.affiliation: Department of Pathology & Medical Biology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Mirjam C
authors.initials: MC
authors.lastname: Boelens
authors.forename: Klaas
authors.initials: K
authors.lastname: Kok
authors.forename: Pieter
authors.initials: P
authors.lastname: van der Vlies
authors.forename: Gerben
authors.initials: G
authors.lastname: van der Vries
authors.forename: Hannie
authors.initials: H
authors.lastname: Sietsma
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg