Familial occurrence of colon and uterine carcinoma and of lymphoproliferative malignancies.II. Chromosomal and immunologic abnormalities

Abstract

Cytogenic and immunologic studies were performed on 20 members of a family who had an increased susceptibility to carcinomas of the colon, uterus and of lymphoproliferative malignancy. Chromosomal abnormalities such as small G and/or long submetacentric marker chromosome and other aberrations were observ.ed in members who had cancer as well as some asymptomatic siblings. In addition, impairment of T cell function was noted in many of the members suggesting that defective cell-mediated immunity, which also may be genetically determined, played an important role in the expression of this disease. Cancer 3 9 : 1 2 29-1 23 6, 19 7 7. ITH T H E RECOGNITION OF INCREASED FRE-W quency of malignancy in patients with immune deficiency, attention has been directed to the study of immunologic functions in family members and patients with various familial car-cinomas and lymphoproliferative disorders. It has been shown recently that subclinical immune defects were present in healthy relatives of patients with familial gastric cancer, non-Hodgkin's lymphoma, '' and chronic lymphocy

Role of tumor suppressor genes in the development of adult T cell leukemia/lymphoma (ATLL)

“…255,256,269 Development of lymphoid tumors such as ALL, CLL, and malignant lymphomas was also reported in human HNPCC kindreds. [270][271][272][273] These observations imply that defects in the mismatch repair apparatus may cause accumulation of mutations in key oncogenes or tumor suppressor genes as well as in microsatellite sequences, thus contributing to the development of tumors. 250,251,274 However, the proportion and spectrum of sporadic cancers associated with mutations in mismatch repair genes has not been clearly elucidated at this time.…”

Non-Hodgkin's Lymphoma in a Patient with Probable Hereditary Nonpolyposis Colon Cancer

“…It has been reported that the development of lymphoma or leukemia is uncommon in HNPCC kindreds, and its relative risk is estimated as low. 8,9 However, lymphocytic neoplasms have been observed in patients with Lynch syndrome Type II 12,13 in addition to those with Muir-Torre syndrome (MTS) [28][29][30][31] and Turcot's syndrome 32 (Table 2); the latter two syndromes have been determined to be distinct phenotypes of HNPCC. The MTS 33, 34 is clinically characterized by the association of sebaceous gland tumors (adenoma, epithelioma, or carcinoma) with cancer(s) of internal organs, including the colon and rectum.…”

“…32 The hematologic malignancies associated with HNPCC and its related syndromes include lymphocytic leukemia, both acute and chronic, nonHodgkin's lymphoma, and lymphosarcoma ( Table 2). [11][12][13][28][29][30][31][32] The reported case of Burkitt's lymphoma 13 is exceptional in that this type of lymphoma is believed to result, at least in part, from Epstein-Barr virus infection and thus is not likely to be related to the HNPCC syndrome. Of 19 HNPCC kindreds in which hematologic neoplasms were diagnosed, only four patients, including our patient, presented with colon cancer.…”

“…Of 19 HNPCC kindreds in which hematologic neoplasms were diagnosed, only four patients, including our patient, presented with colon cancer. 12,29,32 It is noteworthy that although HNPCC tumors are reported to be less aggressive than their sporadic counterparts, [40][41][42][43] most of the associated lymphocytic tumors were fatal in the patients with known outcome. This might account, in part, for the rareness of the reported association of HNPCC with leukemia or malignant lymphoma.…”

“…1,2,[8][9][10] Malignant neoplasms of the hematopoietic system have appeared rarely in the spectrum of HNPCC-associated tumors, 8,9 and only a few cases have been reported. [11][12][13] We describe here a probable HNPCC patient in whom a non-Hodgkin's malignant lymphoma developed after curative resection of ascending colon cancer. A recent experimental study 14 showed that lymphoid tumors frequently develop in mice lacking MSH2, a DNA mismatch repair gene.…”