Loss of heterozygosity of 17p13, with possible involvement of ACADVL and ALOX15B, in the pathogenesis of adrenocortical tumors.

OBJECTIVE

To determine the minimal common region of loss on 17p13 in a cohort of adrenocortical carcinomas (ACCs) (defined by a Weiss score > or =3) and adrenocortical adenomas (ACAs) (defined by a Weiss score <3) and subsequently to assess 3 genes in this region that could be involved in adrenocortical tumorigenesis.

BACKGROUND

Loss of heterozygosity (LOH) of 17p13 has been demonstrated to occur more frequently in ACCs compared with ACAs.

METHODS

Using 12 microsatellite markers across 17p13, LOH analysis was performed on 37 paired blood and adrenocortical tumor samples (23 ACC and 14 ACA samples) to determine the minimal common region of loss for ACCs and ACAs. From this minimal region of loss, 3 genes were selected for quantitative real time reverse transcription polymerase chain reaction analysis on 20 ACCs and 30 ACAs.

RESULTS

LOH at 17p13 was found in 74% of ACCs compared with 14% of ACAs. There was a 10.4-Mb common minimal region of loss in ACCs whereas no minimal region of loss in ACAs could be demonstrated. Expression of Acyl coenzyme-A dehydrogenase very long chain (ACADVL) and Arachidonate 15-lipoxygenase second type (ALOX15B) was significantly down-regulated in ACCs compared with ACAs whereas there was no difference in expression of Potassium channel tetramerization domain containing 11 (KCTD11) in ACCs and ACAs.

CONCLUSIONS

We demonstrated a minimal common region of loss of 10.4-Mb on 17p13 in ACCs and within this region, we found that ACADVL and ALOX15B expression are good discriminators between ACCs and ACAs.