Supplementary Table 1 Other Hereditary Cancer Syndromes with Some Gastrointestinal Involvement

Supplementary Table 1 Other hereditary cancer syndromes with some gastrointestinal involvement.61 Syndrome Gene(s) Inheritance Component Features other than component (chromosomal pattern gastrointestinal gastrointestinal neoplasms locus) neoplasms Malignant Benign neoplasms neoplasms and other features Ataxia ATM (11q22.3)b AR Pancreas and Non-Hodgkin’s Cerebellar ataxia; telangiectasia stomach cancers lymphoma; choreoathetosis; leukemia; breast dysarthria; endocrine and ovarian dysfunction; cancer; immunodeficiency; melanoma telangiectasias Bannayan-Riley- PTEN (10q23)b AD Hamartomas Same as Cowden syndrome Ruvalcaba (juvenile, Cowden features plus proximal syndrome ganglioneuromas, syndrome myopathy; joint lipomas, hyperextensibility; inflammatory) pectus excavatum; throughout scoliosis; pigmented gastrointestinal macules on penis; tract mental retardation and/or developmental delay Beckwith- BWS (11p15) b Sporadic with Gastric teratoma; Wilm’s tumor; Exomphalos; Wiedemann occasional hepatoblastoma; adrenocortical macroglossia; syndrome AD hepatocellular carcinoma; gigantism; mental carcinoma rhabdomyosarco retardation ma; neuroblastoma Bloom syndrome BLM/RECQL3 AR Esophageal, gastric Non-Hodgkin’s Severe growth (15q26.1) b and colon cancer lymphoma; acute deficiency; “butterfly leukemia; oral, rash”; malar hypoplasia; laryngeal, lung, nasal prominence; small skin, breast and mandible; cervical cancers dolichoencephaly Blue rubber bleb TIE2 (9p21)? AD Gastrointestinal None Blue or green bladder- nevus syndrome tract hemangiomas like skin hemangiomas; hemangiomas of eyes, pharynx and uterus Cowden PTEN (10q23) b AD Hamartomas Breast, uterine, Macrocephaly; syndrome (juvenile, thyroid (papillary mucocutaneous lesions ganglioneuromas, & follicular), (papillomatous papules, lipomas, ovarian, renal acral/plantar keratoses, inflammatory) and bladder trichilemommas); throughout (transitional cell) Lhermitte-Duclos gastrointestinal cancers; disease; fibroids; benign tract melanoma breast and thyroid disease; meningioma Familial carcinoid SDHD (11q23) b AD Intestinal and None None syndrome Others? appendiceal carcinoid tumors; malignant carcinoid tumor of the ileum

Fanconi anemia At least 13 AR Esophageal, anal MDS; leukemia; Duodenal atresia; different genes; and hepatocellular head/neck, intestinal malrotation; of note: FANCD1 carcinoma cervix, vulva and skeletal anomalies; skin (BRCA2b) and multiple other hyperpigmentation; FANCN (PALB2) solid tumors renal anomalies; microcephaly; mental retardation Gorlin syndromea PTCH1 (9q22.3)b AD Lymphomesenteric Basal cell Jaw cysts; palmar and cysts (often carcinomas plantar pits; cardiac and calcified); stomach ovarian fibromas; hamartomas meningiomas; tall stature; macrocephaly; frontal bossing; hypertelorism; skeletal malformations; developmental delay Hereditary breast BRCA1 (17q21) b AD Pancreas, bile duct Female and male None and ovarian BRCA2 (13q12) b and gallbladder breast, ovarian cancer syndrome cancers; colon and prostate and/or gastric cancer; cancers?67 melanoma Hyperparathyroidi HRPT2 (1q25) b AD Pancreatic cancer Parathyroid and Hyperparathyroidism; sm-jaw tumor renal (papillary) solitary parathyroid syndrome carcinoma; adenoma; renal cortical Wilms tumor adenoma; Hurthle cell thyroid adenoma; renal cysts; renal hamartomas; multiple ossifying fibromas of the mandible and maxilla Li-Fraumeni TP53 (17p13.1) b AD Colorectal, Sarcoma; breast, None syndrome stomach and adrenocortical pancreatic cancer and brain camcers; leukemia; lymphoma; many other cancers Multiple RET (10q11.2) b AD Ganglioneuromatos Medullary thyroid Marfanoid habitus; endocrine is of the intestine cancer; mucosal neuromas; neoplasia type 2b pheochromocyto “blubbery” lips; ma hyperparathyroidism/par athyroid adenomas NAME syndrome CNC2 (2p16) AD Colorectal and Large cell Carney Complex PRKAR1A pancreatic cancer calcifying Sertoli- (cardiac myxoma, spotty (17q23)b Leydig tumors; pigmentation and Others? liposarcomas; cutaneous myoxmas, testes and and pituitary and thyroid cancer adrenocortical carcinomas) and LAMB in addition to features described in the acronym Tuberous TSC1 (9q34)b AD Hamartomatous Astrocytomas; Facial angiofibromas; sclerosis TSC2 (16p13.3)b rectal polyps Wilm’s tumor; ungual fibromas; renal cell shagreen patch; cortical carcinoma tubers; subependymal nodule or giant cell tumors; retinal hamartomas; cardiac rhabdomyomas; renal angiomyolipoma; lymphangiomyomatosis; cognitive disability von Hippel- VHL (3p25)b AD Pancreatic cysts Retinal and CNS endolymphatic sac Lindau syndrome and cystadenomas; hemagioblastom tumors; renal cysts islet cell tumors as; and PNET pheochromocyto mas; paragangliomas Xeroderma 7 different genes AR Stomach cancer Basal and Severe freckling or pigmentosum squamous cell blistering; irregular carcinomas; pigmentation; abnormal cutaneous sensitivity to UV light; angiosarcomas; poikilodermas; leukemia; solid epitheliomas; angiomas; tumors fibromas; keratoacanthomas and keratoses aAlso known as nevoid basal cell carcinoma syndrome. bGenes for which there is a commercially available genetic test.27 Abbreviations: AD, autosomal dominant; AR, autosomal recessive; LAMB, lentigines, atrial myxomas, mucocutaneous myxomas and blue nevi; MDS, myelodysplastic syndrome; NAME, nevi, atrial myxoma, myxoid neurofibromas, and ephelides; PNET, primitive neuroectodermal tumor.