Loss of heterozygosity on chromosome arm 17p in small cell lung carcinomas, but not in neurofibromas, in a patient with von recklinghausen neurofibromatosis

Abstract

Background. It has been suggested that the genetic abnormality responsible for von Recklinghausen neurofibromatosis (NF1) increases a patient's risk of various kinds of malignancies. The incidence of small cell lung carcinoma (SCLC) as a complication of NF1, however, is rare. To clarify the relationship between NF1 and SCLC, possible loss of heterozygosity of chromosome 17 in a patient with SCLC combined with NF1 was analyzed. Methods. Possible loss of heterozygosity for chromosome 17 was analyzed by a molecular genetic approach using several chromosome 17‐specific polymorphic DNA markers. Results. In both primary tumor and metastatic tumors of SCLC, loss of heterozygosity was detected on chromosome arm 17p, but not on 17q. Loss of heterozygosity, however, was detected on neither 17p nor 17q in neurofibromas and normal tissue. Conclusions. The formation of SCLC may result from several genetic alterations, including inactivation of tumor‐suppressor gene on chromosome 17p, most likely P53, although it still is unknown whether or not a mutation of the NF1 gene on 17q was involved in the development of SCLC in this patient.

Clonal and Parallel Evolution of Primary Lung Cancers and Their Metastases Revealed by Molecular Dissection of Cancer Cells

“…In these three SCLC cases, tumors and normal lung tissues were stored at À80jC without fixation until DNA extraction. Cancerous and noncancerous cells of the three SCLC cases (cases 6-8) were macrodissected, and genomic DNAs were prepared as described previously (23,24). This study was undertaken according to the guidelines for medical research in Japan.…”

Carcinosarcoma of the lung associated with neurofibromatosis type 1: a case report

“…Recently, lung malignancies reported in association with neurofibromatosis have been reported infrequently (3)(4)(5)(6)(7). Carcinosarcoma of the lung is a rare tumor, constitutes approximately 0.2-0.27% of all lung cancers, and has a poor clinical outcome (8).…”

Novel Mutations of Neurofibromatosis Type 1 Gene in Small Cell Lung Cancers

“…Several cases of lung cancer in patients with NF1 have been reported in Japan and other countries (see above). As quoted below in more detail, Shimizu et al 15 failed to detect a deletion in the NF1 gene in a rare case of small cell lung carcinoma occurring in an NF1 (Table 2). Cases 1, 6, and 7 had abnormal bands (see Results for more details) Fig.…”

“…In fact, a number of malignant myeloid disorders have been reported; 19,23,24 however, several attempts have failed to detect mutations in the GRD of NF1 gene in myeloid malignancies without NF1 phenotypes. 22,25 Shimizu et al 15 reported a rare case of small cell lung carcinoma developing in a subject with NF1. Using several chromosome 17-specific polymorphic DNA markers, they looked for NF1 deletions in both primary tumor and metastatic tumors, without success.…”

“…Since then, three sources have published reports on five cases of lung cancers associated with NF1. [13][14][15] In the present study, we screened 37 cases of lung cancer in an attempt to detect possible mutations within the functional GTPase-activating protein-related domain (GRD) of the NF1 exon 24, being the so-called FLR exon. We identified three mutations in three cases of small cell carcinoma, two of which involved amino acid substitution (Glu AE Gly).…”