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Loss of Heterozygosity of 17p13, With Possible Involvement of ACADVL and ALOX15B, in the Pathogenesis of Adrenocortical Tumors

Soon, Patsy S. H. MBBS, FRACS*; Libe, Rossella MD†‡§¶∥; Benn, Diana E. PhD*; Gill, Anthony MBBS, FRCPA**; Shaw, Janet BSc, BA*; Sywak, Mark S. MBBS, FRACS††; Groussin, Lionel MD, PhD†‡§∥; Bertagna, Xavier MD†‡§∥; Gicquel, Christine MD, PhD‡‡; Bertherat, Jerome MD, PhD†‡§∥; McDonald, Kerrie L. PhD*; Sidhu, Stan B. PhD, FRACS††; Robinson, Bruce G. MD, FRACP§§

doi: 10.1097/SLA.0b013e318153ff55
Original Articles
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Objective: To determine the minimal common region of loss on 17p13 in a cohort of adrenocortical carcinomas (ACCs) (defined by a Weiss score ≥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.

Summary Background Data: 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.

A 10.4-Mb common minimal region of loss of heterozygosity on 17p13 was identified in adrenocortical carcinomas. ACADVL and ALOX15B are 2 genes within this region that are significantly differentially expressed between adrenocortical carcinomas and adenomas.

From the *Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, and University of Sydney, New South Wales, Australia; †INSERM U567, Endocrinology, Metabolism, and Cancer Department, and ‡CNRS UMR8104, Institut Cochin; §Université Paris-Descartes, Site Cochin-Port-Royal; ¶Oncogenetic Unit, and ∥Department of Endocrinology, Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France; Departments of **Anatomical Pathology, and ††Endocrine and Oncology Surgery, Royal North Shore Hospital and University of Sydney, New South Wales, Australia; ‡‡Assistance Publique Hôpitaux de Paris, Hôpital Trousseau, Service d’Explorations Fonctionnelles, Paris, France; and §§Department of Endocrinology, Royal North Shore Hospital, and University of Sydney, New South Wales, Australia.

Supported by the National Health and Medical Research Council of Australia, New South Wales Cancer Institute, Royal Australasian College of Surgeons and Department of Endocrine and Oncology Surgery, Royal North Shore Hospital, Sydney, Australia (to P.S.H.S.). This work is also supported in part by the Plan Hospitalier de Recherche Clinique to the COMETE network Grant AOM 02068 (to J.B.).

The first two authors contributed equally to this work.

Reprint: Stan Sidhu, PhD, FRACS, Department of Endocrine and Oncology Surgery, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia. E-mail: stansidhu@nebsc.com.au.

© 2008 Lippincott Williams & Wilkins, Inc.