Kit, Nras, Braf, And Pten Alterations In Acral Lentiginous Melanomas

8588 Background: Acral lentiginous melanoma (ALM) accounts for ~5% of all melanomas. ALMs are often located on palms, soles and under nails. Patients with ALM are significantly older at diagnosis and have a poorer prognosis than patients with other types of cutaneous melanoma. We analyzed a large series of ALMs from Swedish patients to better define the frequency of KIT, BRAF, NRAS, and PTEN mutations in ALM. The effect of mutation status on tumor and patients characteristics was also studied. Methods: A total of 77 primary ALMs and 8 paired metastases were analyzed. Laser capture microdissection was used to dissect tumor cells from formalin-fixed paraffin-embedded tissue. Tumors were screened for mutations in the KIT (exons 11, 13, 17 and 18), NRAS (exons 1 and 2), BRAF (exons 11 and 15) and PTEN (exons 1, 3-6, 10, 11 and 12) genes by direct sequencing. Results: There were 42 females and 35 males with a median age at diagnosis of 71 years. The most common location was the feet (60.5%), followed by subungual sites (34.2%). Overall, mutations in KIT, NRAS and BRAF were detected in 11.8%, 14.5% and 16.0% of the ALMs, respectively. In no case were KIT, NRAS and BRAF mutations detected in the same tumor. For 8 primary ALMs the corresponding metastases were available for analysis. In five metastases the same KIT (n=3) or BRAF (n=2) mutation was detected as in the primary ALMs, suggesting that the KIT and BRAF mutations had occurred before metastasis. BRAF and NRAS mutations were significantly more common in females (P=0.044). ALMs with NRAS and BRAF mutations were more commonly located on the feet compared with KIT mutated ALMs which were more frequent on subungual sites (P=0.041). Other clinicopathological features such as age at diagnosis, thickness, ulceration, histological subtype and Clark’s level showed no significant correlation with the mutation status. A subset of 25 tumors was evaluated for mutations in the PTEN tumor suppressor gene. One tumor was found to carry a nonsense mutation (W111X). To our knowledge, this is the first description of a PTEN mutation in ALM. Conclusions: Our results confirm the presence of KIT, NRAS and BRAF mutations in ALM. KIT, NRAS and BRAF mutation status associated significantly with anatomical site. PTEN mutations seem to be rare in ALMs.