c-<i>kit</i> Mutation in Generalized Lentigines Associated with Gastrointestinal Stromal Tumor

Abstract

We describe the case of a 59-year-old Japanese woman presenting with generalized lentigines without systemic anomalies. She had a medical history of gastrointestinal stromal tumors (GISTs), in which gain-of-function mutations of the c-kit gene had recently been found. We detected a point mutation at codon 557 in exon 11 of leukocyte DNA from the patient. The stem cell factor-type III receptor tyrosine kinase pathway plays important roles in the regulation of melanocyte proliferation and differentiation. We speculate that the generalized lentigines of the patient may be caused by melanocyte proliferation due to the c-kit gene mutation.

Familial gastrointestinal stromal tumors, lentigines, and café‐au‐lait macules associated with germline c‐kit mutation treated with imatinib

“…Out of the 35 familial GIST, including the present kindred, described so far, 22 carry mutations in exon 11 (encoding the juxtamembrane domain), seven in exon 13 (kinase I domain), four in exon 17 (kinase II domain), one single family, and one single patient in exons 8 and 9 (extracellular juxtamembrane domain), respectively …”

“…Familial GISTs, associated with germline c‐kit mutation, are a very rare inherited condition described so far in 34 different families . The KIT receptor is expressed on erythrocytes, melanocytes, germ cells, mast cells, and interstitial cells of Cajal (ICC).…”

“…Familial GISTs, caused by germline gain‐of‐function c‐ kit mutations, represent a rare autosomal dominant condition characterized by multiple primary neoplasms, involvement of several family members, early presentation, and additional clinical features, including hyperpigmentation, mast cell disease, and dysphagia . Gain‐of‐function mutations of c‐kit produce a constitutive, ligand independent activation of the receptor and downstream pathways .…”

Laugier-Hunziker syndrome: a case of asymptomatic mucosal and acral hyperpigmentation

“…Gain-of-function mutations in the Kit oncogene, encoding c-Kit, are associated with chronic myeloid leukemia and gastrointestinal stromal tumor (GIST) development [10]. Interestingly, there are reported cases of germline mutation of c-Kit demonstrated in a patient with numerous lentigines and GISTs [10].…”

“…Interestingly, there are reported cases of germline mutation of c-Kit demonstrated in a patient with numerous lentigines and GISTs [10]. It is possible that the gain-of-function mutation of c-Kit pathway may activate the downstream pathways and promote proliferation of melanocytes, leading to the melanocytic hyperplasia involved in formation of mucosal and acral macules of LHS.…”