Table 1.

Suggested matrix for genetic screening of suspected malignant mesothelioma cases.

Patient type	Specifc genetic lesions	Rationale and possibly associated clinical eatures
All Patients	Deletions in tumor tissue DNA at 1p21-p22, 3p21.3, 9p14/p16, 6q14-q21, 6q16.6-q21, 6q21-q23.2, 6q25, 15q11.1-q15; and loss of a copy of chromosome 22	Most commonly associated genetic lesions identified in mesothelioma but overlapping with other cancer types. Monitor statistical associations to identify which specific deletions are most specific and diagnostic for general and site-specific mesothelioma
Patients with prominent epithelioid histology and primary midline or mediastinal tumor occurrence	Germ cell tumor markers in tumor tissue: iso12p, often multiple copies; widespread gene loss across most chromosome arms, and non-random gains in chromosomes 1, 7, 12, 21, 22, and X	Germ cell tumors can metastasize widely, and extragonadal germ cell tumors are known to occur in nodes and tissues along the embryonic urogenital ridge from the cranium to the presacral region (C6 to L4) due to abnormal germ cell migration. Treatment and prognosis may be very different compared to primary mesothelioma. Clinical correlates may include history of cryptorchidism and family history of testicular cancer or male sibling leukemia or lymphoma
Patients with epithelioid histology and primary peritoneal tumor occurrence and a family history or personal history of breast and/or ovarian cancer	Testing of tumor tissue and somatic cells for mutations in BRCA-1 and BRCA-2 for meso with history of ovarian or breast cancer; mutations at 2p16, 3p21.3, 7p22 for history of multiple endocrine cancer; and del(22q11.2) and trisomy 13, 15, 18 or 21 and for peritoneal meso with heart valve defects	Serous epithelioid cancers from mullerian tissues can present as peritoneal metastases from occult tumors of mullerian tissues (e.g., ovarrian surface epithelium, fallopian tubes and fimbria) and are difficult to distinguish from mesothelioma without thorough pathological evaluation. Serous carcinomas may occur sporadically or with familial syndromes including Breast Ovarian Cancer Syndrome, Site Specific Ovarian Cancer Syndrome, and Hereditary Non-Polyposis Colon Cancer
Patients with prominent spindle cell histology and possible history of severe synovial trauma and/or recurrent synovial growths	Synovial sarcoma markers in tumor tissue: translocation (x;18) leading to SSX1 or SSX2 fusion gene transcripts	Synovial sarcomas generate from mutation of mesenchymal tissues, can metastasize to locations mimicking true mesothelioma, and can have widely varied clinical presentation and prognosis. Genetic tracking of these tumors may assist to better characterize primary site, treatment and prognosis. Recurrent synovial or ganglionic cysts, and severe or repeated trauma to synovial tissues may reflect higher risks
Patients with personal and/or family history of certain additional primary cancers (e.g., thyroid, prostate, testes, breast, ovary, pancreas, GI tract, ureter, endometrium)	Somatic cell mutations: 11q13 for history of possible multiple endocrine neoplasia/ Zollinger-Ellison Syndrome, MEN-1/ZES; and 2p16, 3p21.3, 7p22 mutations for history of possible hereditary non-polyposis colon cancer, HNPCC	In advanced stages of invasive/metastatic cancers from MEN-1 or HNPCC, chromosomal instability may lead to histopathologic features that mimick mesothelioma. Genetic tracking may assist to better characterize primary site, treatment and prognosis. MEN-1/ZES includes diagnostic gastrinomas of duodenum/pancrease with intractable peptic ulcer disease often requiring gastrectomy. HNPCC includes diagnostic carcinoid tumors of duodenum and ascending colon